Dictionary of cardiac metabolism

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Accuracy

  • Accuracy is a measure of the agreement/closeness of a measured value to the true/actual value. With respect to diagnostic accuracy measures, the area under the receiver operating characteristic (ROC) curve can be used as a measure of the accuracy of a diagnostic test.

Acetyl-coenzyme A (CoA)

  • Acetyl-coenzyme A (CoA) is an important intermediate ofmany biochemical pathways. For instance, acetyl-CoA isan important product of the mitochondrial metabolism offatty acids and carbohydrates. Acetyl-CoA produced fromthese carbon substrates feeds into the mitochondrialtricarboxylic acid cycle (or Krebs cycle), which whencoupled to the mitochondrial electron transport chainresults in the production of energy (in the form of ATP).

Acetyl-coenzyme A carboxylase (ACC) 2

  • Acetyl-coenzyme A carboxylase (ACC) is a key enzymeinvolved in both the synthesis and metabolism of fatty acids.ACC produces malonyl coenzyme A, which is both a substratefor fatty acid biosynthesis and a potent inhibitor ofmitochondrial fatty acid uptake. Heart and muscle primarilyexpress ACC2, which is the isoform of ACC that is thought tobe primarily involved in the regulation of fatty acid oxidation.

Acyl-CoA synthetase (MHC-ACS)

  • Long chain acyl-CoA synthetase is one of the first enzymesin the fatty acid metabolic pathway. It converts long chainfatty acids to long chain acyl-CoA within the cell. Longchain acyl-CoA is then either metabolized by themitochondria to produce energy, or is used to producemembrane and cellular lipids. MHC-ACS refers to anexperimental approach to selectively express acyl-CoAsynthetase (ACS) in muscle. This is achieved by linkingthe ACS gene to the myosin heavy chain (MHC) promoter.The production of transgenic mice from embryonic stemcells that contain the MHC-ACS gene will result in micethat overexpress ACS targeted to muscle.

Acylation stimulating protein (ASP)

  • Acylation stimulating protein (ASP) is an adipocytederivedprotein that upregulates triacylglycerol synthesisin adipocytes. ASP has recently been suggested to play animportant role in the regulation of lipoprotein metabolismand triacylglycerol storage. ASP also appears to have a rolein the regulation of energy balance.

Adeno-associated virus

  • Adeno-associated virus (AAV) is a nonpathogenic human virus that belongs to the Parvoviridae family. Replication-defective AAV, which is devoid of all viral genes, is utilized as a gene transfer vector. AAV vectors do not integrate into the host genome. AAV vectors have several desirable properties for in vivo gene transfer, including low immunogenicity, lack of inflammatory response following in vivo administration, and the ability to deliver genes into postmitotic cells (eg, cardiac myocytes) with high efficiency.

Adenosine

  • Adenosine is an endogenous purine nucleoside, formed from the breakdown of intracellular ATP in response to cellular stresses including hypoxia, and ischemia. Adenosine can gain access to the extracellular/interstitial space via nucleoside transporters located in the plasma membrane, and subsequently activate a variety of cell surface, Gprotein coupled receptors (e.g. A1-, A2a- , A2b-, and A3-adenosine receptors) to exert its biological effects.

Adenylate cyclase

  • Adenylate cyclase is an enzyme that catalyzes theconversion of ATP to cAMP. cAMP is an important secondmessenger molecule involved in signal transduction.Adenylate cyclase is activated or inhibited by G proteins,which are coupled to membrane receptors, such as the ß-adrenergic receptor.

Adhesion molecules

  • Adhesion molecules are cell surface proteins that bind other cells or the extracellular matrix during the process of cellular adhesion.

Adipokines

  • Adipokines is a term that is used to collectively describe avariety of signalling molecules that are released fromadipose tissue. Examples of adipokines includeadiponectin, and cytokines such as TNF-1α.

Adiponectin

  • Adiponectin is an adipokine that is released from adipose tissue. It is an important signaling molecule that acts centrally at the level of the hypothalamus to decrease food intake, and peripherally to modify fatty acid and glucose metabolism. Low levels of adiponectin are associated with obesity and insulin resistance.

Adipophilin

  • Adipophilin is a protein that is involved in lipid transportor storage. Adipophilin, which was initially described inadipocytes, is associated with lipid accumulation in cells.It is found in many cells and may be a new marker for theidentification of specialized differentiated cells containinglipid droplets and for diseases associated with fataccumulatingcells.

Adipsin

  • Adipsin is one of a number of physiologically importantproteins excreted by adipocytes. Adipsin has a role in theregulation of energy intake and storage, and works withacylation stimulating protein to regulate lipoproteinmetabolism and triacylglycerol storage. In the gut, adipsinfacilitates removal of lipid from chylomicrons.

Agouti protein

  • Agouti protein is an endogenous antagonist of melanocortinreceptors that have been implicated as part of thehypothalamic mechanism that mediates leptin-inducedhypophagia. The agouti protein has a role in controlling energyhomeostasis and possibly human pigmentation.

Akt-1

  • Akt, which is sometimes called protein kinase B (PKB), is an intracellular kinase that is important in a number of cellular functions, including regulation of glucose metabolism and cell growth. It is a kinase in the insulin signaling pathway, and insulin activation of Akt results in glucose transporter-4 (GLUT-4) translocation to the cell membrane, thereby stimulating glucose uptake. Overexpression of Akt in the heart can cause a marked hypertrophy of the muscle.

Aldehydes

  • An aldehyde is either a functional group consisting of aterminal carbonyl group or a compound containing a terminalcarbonyl group. Aldehydes such as malondialdehyde are alsoproducts of free radical injury. Lipid hydroperoxidesdecompose to form a variety of products includingmalondialdehyde, which is used as an indicator of theoxidative damage of cells and tissues.

Algogenic

  • Is a medical term that refers to any stimulus or situationthat causes pain.

Allele

  • An allele is one of two or more alternative forms of a geneat the same site in a chromosome. This determines thealternative characteristic of the inheritance.

Allosteric regulation of enzymes

  • Allosteric regulation of an enzyme involves the change inthe shape and activity of an enzyme that results frommolecular binding with a regulatory substance at a siteother than the enzymatically active one. An example ofthis is binding of 5-adenosine monophosphate (AMP) to aregulatory site on AMPactivated protein kinase that resultsin an activation of the enzyme.

Alogliptin

  • Alogliptin is an orally taken dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Takeda Pharmaceutical Company for the treatment of type 2 diabetes under the trade name Nesina in the United States, and Vidipia in Europe. Unlike saxagliptin, alogliptin is not associated with an increased risk for hospitalization for heart failure.

Alogliptin

  • Alogliptin is an orally taken dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Takeda Pharmaceutical Company for the treatment of type 2 diabetes under the trade name Nesina in the United States, and Vidipia in Europe. Unlike saxagliptin, alogliptin is not associated with an increased risk for hospitalization for heart failure.

Alpha-myosin heavy chain

  • Muscle is made up of interacting thick and thin filamentsthat slide past each other to produce muscle contraction.The thick filaments consist mainly of myosin. Myosin is avery large molecule made up of two identical heavy chains(alpha-myosin heavy chains) and four light chains. Thealpha-myosin heavy chain consists of an alpha helicalcoiled rod and a globular region.

Alphatocopherol

  • Alphatocopherol (or vitamin E) is an antioxidant that protectscell membranes from free radical-induced lipidperoxidation. Ubiquinone can recycle radical forms ofvitamin E, thereby also protecting membrane phospholipidsagainst peroxidation.

AMP-activated protein kinase (AMPK)

  • AMPK is a key kinase that controls many cellular processes, particularly pathways involved in cellular energy status. AMPK is activated during metabolic stress, where it then can either activate energyproducing pathways or inhibit energy-consuming pathways. For these reasons, it has been termed a “fuel gauge” of the cell.

Amyloidosis

  • A large, heterogeneous group of diseases characterized by themisfolding of extracellular protein. Misfolding occurs in parallel or as an alternative to physiological folding and generates insoluble protein aggregates (bundles of β-sheet fibrillar protein). Despite possessing heterogeneous structures and functions, fibrillar proteins are morphologically similar. Organ dysfunction results from the deposition and cytotoxic effects of insoluble amyloid proteins.

Anaerobic glycolysis

  • Anaerobic glycolysis is the first part of the metabolicpathway for glucose. The glycolysis pathway metabolizesglucose to pyruvate, and in the process produces energy inthe form of ATP. The glycolytic pathway can be considered“anaerobic” since no oxygen is required for the productionof ATP (unlike aerobic mitochondrial metabolism, whichrequires oxygen).

Angiogenesis

  • Angiogenesis is the physiological process by which new blood vessels are formed from preexisting blood vessels. Angiogenesis is a critical process in normal growth and development, wound healing, and repair, as well as in the formation of granulation tissue.

Angiopoietin

  • Angiopoietin is an important regulator of endothelial cellsurvival. One of the actions of angiopoietin reducesvascular permeability mediated by vascular endothelialgrowth factors.

Angiotensinogen

  • The renin-angiotensin system is widely known for itsimportance in controlling blood pressure, electrolytehomeostasis, and volume regulation. Angiotensinogen isan early intermediate of this pathway, and polymorphismsin this gene contribute to the pathogenesis of bothhypertension and cardiovascular disease.

Annexin V

  • Annexin V, a calcium-binding protein, is widely present invarious organs and tissues. Assaying annexin V is a method ofassessing the degree of tissue apoptosis. High levels of plasmaannexin V in patients with acute myocardial infarction, cardiacarrest, or severe trauma have also been suggested to reflect theseverity of damage to the myocardium.

Antagomir

  • An antagomir is a chemically modified antisense oligonucleotide. Typically, a locked nucleic acid modification is utilized to restrict the ribose moiety of the nucleotide into a conformation ideal for complementary Watson-Crick binding. This modification confers long-lasting stability to the antagomir. Antagomirs bind and deplete microRNAs from cells, thereby preventing microRNA-induced messenger RNA degradation and translational inhibition.

Anthracyclines

  • Anthracyclines are a class of antibiotics produced by Streptomyces bacteria. They are effective in the treatment of various types of cancers, some of which include leukemia and lymphomas, but their use is limited due to their cardiotoxic effects. They have three primary mechanisms of action that are involved in mediating their anticancer properties: I) inhibiting DNA and RNA synthesis, 2) inhibiting topoisomerase II, and 3) increasing iron-mediated free radical production.

Anti-C-reactive protein (CRP) activity

  • C-reactive protein (CRP) is a protein that is produced in theacute phase of an inflammatory reaction. Recent interest hasfocused on the measurement of CRP as an indicator ofvarious inflammatory diseases, as well as to assess thedegree of cardiovascular risk. For example, measurement ofCRP has been used to measure inflammation associated withan acute myocardial infarction or unstable angina. Anti-CRPis an antibody against CRP that can be used to assess CRPlevels/activity in the serum of patients.

Anti-tumor necrosis factor-α (TNFα)

  • Tumor necrosis factor-a (TNFα) is a cytokine that hasdiverse actions in the body. With regard to the heart, TNFα binds to cardiac receptors and mediates a number ofcellular processes, including the promotion of apoptosis(programmed cell death), and activation of inducible nitricoxide synthase.

Antimyosin

  • Antimyosin antibody is an antibody that recognizes myosinin muscle cells. Since myosin is intracellular, myocardialuptake of antimyosin antibodies (ie, 111In-antimyosin) isused as a measure of necrotic cell injury.

Apolipoprotein (apo) E

  • Apolipoprotein (apo) E is one of the proteins associatedwith circulating lipoproteins. Polymorphisms in the apo Egene result in the development of atherosclerosis andincrease the risk for heart disease, stroke, and Alzheimer’sdisease.

Apoptosis

  • Referred to as programmed cell death, apoptosis involves a series of events resulting in cellular morphological changes and subsequent death, including cell shrinkage, blebbing, nuclear fragmentation, and chromatin condensation. One of its key features is that, unlike a necrotic cell, the cellular contents do not spill out due to phagocytic cells engulfing the apoptotic cell, which is a primary reason why apoptotic cell death does not result in inflammation.

Arachidonic acid pathway enzymes lipoxygenase

  • The lipoxygenase pathway is an important group of enzymesinvolved in the metabolism of arachidonic acid to leukotrienes.Leukotrienes have diverse biological actions in the body.

Area at risk

  • The area of myocardium at risk of myocardial infarction after an acute coronary artery occlusion.

Arg302Gln amino acid substitution in the gamma-2 regulatory subunit (PRKAG2) of AMPK

  • PRKAG2 is the gene that encodes the gamma2 subunit ofAMP-activated protein kinase (AMPK). Mutations inPRKAG2 have recently been shown to cause cardiachypertrophy, cardiac glycogen accumulation, Wolff-Parkinson White syndrome and conduction system diseasecausing pre-excitation. One of these mutations involvesthe substitution of arginine for glutamine at the 302amino acid position of the gamma2 subunit of AMPK. It isthought that this mutation decreases the activity of AMPKin the heart.

ATP

  • Adenosine-5’-triphosphate (ATP) is a multifunctional nucleoside trisphosphate that acts as the molecular unit of currency in intracellular energy transfer. The primary objective of intermediary metabolism in living organisms is tomaintain a steady supply of ATP required for growth, reproduction, and responding to the stresses (i.e., starvation, exercise) associated with daily living.

ATP-sensitive K+-channels

  • ATP-sensitive potassium (KATP) channels are potassiumchannels that are present in either the plasma membraneof the cell, or the mitochondrial membrane of the cell.These channels are inhibited by ATP, and the KATP in theplasma membrane serve to couple the metabolic status ofthe cell to its membrane potential. KATP regulates anumber of cell actions, including muscle contractility(skeletal, cardiac and vascular smooth muscle). Theopening of sarcolemmal and mitochondrial ATP-sensitiveK(+) (KATP) channels in the heart is believed to mediateischemic preconditioning, a phenomenon whereby briefperiods of ischemia/reperfusion protect the heart againstmyocardial infarction.

ATP-sensitive potassium channels (KATP)

  • KATP are potassium channels gated by ATP present in the sarcolemmal, mitochondrial, and nuclear membranes. Increased ATP levels cause these channels to close, resulting in depolarization.

ATPase

  • An ATPase is a protein that utilizes the hydrolysis of ATP as an energy source to drive the process of primary active transport in which ions are transported against a concentration gradient, or electrical potential.

Autacoids

  • Autacoids are organic substances produced in one celltype that act either on the same cell, or a cell nearby toproduce a biological effect. Nitric oxide (NO) orprostaglandins are examples of autacoids.

Autoantibody

  • An autoantibody is an antigen-binding protein synthesized by the immune system (ie, B cells) that recognizes the body’s normal constituents as “non self”/foreign. Autoantibodies can attack these normal constituents leading to inflammation and tissue damage, and are central contributors to the pathophysiology of autoimmune diseases.

Autoantigen

  • An autoantigen is a substance that, despite being a normal tissue component, is recognized by the immune system (ie, B cells and T cells) as “non self”/foreign and is subjected to an inappropriate cell-mediated and/or humoral immune attack resulting in autoimmunity.

Autoimmunity

  • Autoimmunity is a pathological process characterized by immune system activation (innate and adaptive) against self (ie, non foreign) antigens that ultimately leads to tissue inflammation and damage.

Autophosphorylation

  • Autophosphorylation refers to a situation where a kinasecan phosphorylate an identical kinase.

Bamiphylline

  • Bamiphylline is a specific A1 adenosine receptorantagonist. By inhibiting A1 receptors it antagonizes theactions of adenosine on these receptors. This includes anycardioprotective effects of adenosine in the ischemicheart.

Beta-oxidation inhibitors

  • Compounds or drugs that inhibit mitochondrial fatty acid beta-oxidation. They do so primarily by either directly inhibiting mitochondrial fatty acid betaoxidation enzymes (i.e., trimetazidine, an inhibitor of 3-ketoacyl CoA thiolase), or preventing the uptake of fatty acids into the mitochondria (i.e., perhexiline, an inhibitor of carnitine palmitoyl transferase).

Body mass index

  • Body mass index (BMI) is a formula for measuring an individual’s relative weight based on their mass and height and is calculated by the formula BMI = mass in kilogram/(height in meters)2. A healthy BMI is generally considered to be in the range of 18.5 to 24.9, whereas those with BMIs in the 25 to 29.9 range are classified as being overweight, and those with BMIs >30 are classified as obese. Although BMI is frequently used to assess general body mass in patient populations, the BMI does not take into account age, sex, or muscle mass, and it can result in large BMI scores for people that actually have very low body fat percentages, such as body builders.

Body Mass Index (BMI)

  • BMI is a formula for measuring an individual’s relative weight based on their mass and height and is calculated by the formula BMI=( (mass (kg)/(height(m))2 ). A healthy BMI is generally considered to be in the range of 18.5 to 24.9, whereas those with BMIs in the 25 to 29.9 range are classified as being overweight, and those with BMIs >30 are classified as obese. Although BMI is frequently used to assess general body mass in patient populations, the BMI does not take into account age, gender, or muscle mass, and it can result in large BMI scores for people that actually have very low body fat percentages, such as body builders.

Bradykinin

  • Bradykinin is a small peptide of the kinin group ofproteins, consisting of nine amino acids. It is a potentendothelium-dependent vasodilator that causescontraction of non-vascular smooth muscle, increasesvascular permeability and is also involved in themechanism of pain.

C-reactive protein (CRP)

  • CRP is a plasma protein produced by the liver. CRP is a member of the class of acute phase reactants, and its levels rise when inflammatory processes occur in the body. CRP assists in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages. It therefore plays an important role in immunity and defence against infections. Because CRP rises dramatically during inflammation, measurement of its level in the blood can be used as a marker of inflammation.

Calcineurin

  • Calcineurin is a phosphatase that cleaves phosphategroups from proteins. This phosphatase has received aconsiderable research interest in cardiac hypertrophy,since activation of calcineurin can promote cell growthsecondary to dephosphorylation of translocation nuclearfactor of activated T-cell (NFAT). The dephosphorylatedNFAT can then translocate to the nucleus and promote cellgrowth.

Calmodulin

  • Calmodulin is an important molecule that binds calciumand stimulates the activity of calmodulin-dependentkinases. Calmodulin mediates many important reactions inthe cell, including excitation contraction coupling ofmuscle cells.

Calmodulin-dependent fashion

  • Calmodulin is an important molecule that binds calciumand stimulates the activity of calmodulin- dependentkinases. Calmodulin mediates many important reactions inthe cell, including excitation-contraction coupling ofmuscle cells.

CamKll

  • Ca2+/calmodulin-dependent protein kinase II (CaMKII) is akinase that is activated by Ca2+/calmodulin. This kinaseregulates many cellular proteins, many of which are involvedin the regulation of cellular calcium. Activation of CamKII hasalso been shown to induce cardiac hypertrophy.

Carbohydrates

  • These organic molecules contain only carbon, hydrogen, and oxygen, with the ratio of hydrogen to oxygen usually being 2:1. Important circulating carbohydrate energy sources for myocardial metabolism include glucose (C6H12O6) and lactate (C3H6O3).

Cardiac Magnetic Resonance (CMR)

  • CMR exploits the magnetic properties of various atomic nuclei. Cardiac magnetic resonance imaging (CMRI) is a non-invasive imaging modality considered to be the gold-standard for quantifying ventricular mass, structure, volume, and function .

Cardiac magnetic resonance imaging (MRI)

  • An imaging technology that noninvasively assesses function and structure of the cardiovascular system. The technology uses magnetic field and pulses of radio wave energy to image the heart and vasculature.

Cardiomyopathy

  • Cardiomyopathy simply means “heart muscle disease”, and refers to any type of deterioration of heart muscle function. If this dysfunction is due to ischemia, it is referred to as ischemic cardiomyopathy, or if it is due to underlying diabetes, it is referred to as diabetic cardiomyopathy.

Cardioprotection

  • Strategies and treatments for protecting the heart against the detrimental effects of acute ischemia/reperfusion injury on the myocardium.

Cardiotin

  • Cardiotin is a high molecular weight (300 kDa) constituent ofcardiac muscle. It is a structural protein associated with thesarcoplasmic reticulum. The measurement of cardiotin hasbeen used to characterize the morphology of cardiac cells.

Cariporide

  • Cariporide is a drug that inhibits an enzyme called thesodium-hydrogen exchanger. This exchanger exists in themembrane of cells, including the cardiomyocyte, andexchanges intracellular hydrogen for extracellular sodium.Inhibition of this enzyme prevents the accumulation ofsodium inside the cell during ischemia. Cariporide has beentested in clinical trials for use in various forms of ischemicheart disease, and has shown some promise as acardioprotective agent during coronary artery bypass surgery.

Carnitine palmitoyl transferase-1

  • Carnitine palmitoyl transferase-1 (CPT-1) is the ratelimiting enzyme involved in the uptake of fatty acids in the mitochondria. It converts fatty acyl–coenzyme A to fatty acylcarnitine, which is then transported into the mitochondria where it is further metabolized. CPT-1 is a highly regulated enzyme that prevents excess fatty acid from being taken up into the mitochondria.

Carnitine palmitoyl transferase 1 (CPT-1) inhibitors

  • Compounds or drugs that inhibit the mitochondrial outer membrane enzyme CPT-1, which is the ratelimiting enzyme for mitochondrial fatty acid uptake and subsequent beta-oxidation. Therefore, CPT-1 inhibitors inhibit mitochondrial fatty acid beta-oxidation secondary to an inhibition of its uptake into the mitochondria.

Carnitine palmitoyl transferase-1 (CPT-1)

  • Carnitine palmitoyl transferase-1 (CPT-1) is the ratelimitingenzyme involved in the uptake of fatty acids in themitochondria. It converts fatty acyl-coenzyme A to fattyacylcarnitine, which is then transported into themitochondria where it is further metabolized. CPT-1 is ahighly regulated enzyme that prevents excess of fatty acidsfrom being taken up into the mitochondria.

Carnitine-acylcarnitine translocase

  • Carnitinue acylcarnitine translocase is an importantenzyme involved in the mitochondrial uptake of fattyacids. Carnitine-acylcarnitine translocase is the enzymeresponsible for translocating acylcarnitine across themitochondrial membrane in exchange for carnitine.

Carotenoids

  • Carotenoids are natural antioxidants that are abundant infruit and vegetables. It has been proposed that theepidemiological association between high fruit andvegetable consumption and lower cancer rates may berelated to an increased consumption of carotenoids.

Catalase

  • Catalase is a common enzyme that functions to catalyzethe decomposition of hydrogen peroxide to water andoxygen. Catalase is an important anti-oxidant enzyme thatprotects the cell from free radical injury.

Catechin

  • Catechin is a flavonoid, sometimes called flavanol. Catechinhas antioxidant properties and can prevent free radical injury.It is present in grapes and has been suggested to contributeto the antioxidant properties of wine.

Caveolin

  • Caveolie are invaginations in the plasma membrane of cellsthat represent subcompartments of the plasma membrane.Caveolins are caveolie coat proteins. Recent interest hasfocussed on the role of G-proteins associated with caveolins asa mechanism for transmembrane signalling.

CD34+ cells

  • CD34+ cells are hematopoietic stem cells that express the protein CD34, which is also known as hematopoietic progenitor cell antigen CD34. CD34 is a protein identified by the cluster of differentiation nomenclature used to identify cell surface molecules, and it is a cell surface glycoprotein that has been shown to participate in cell-cell adhesion. Identification of CD34+ cells is often used as a marker for activated hematopoietic stem cells.

Ceramide

  • Ceramides are specialized lipids that are derived from sphingomyelin and glycosphingolipids present in plasma membrane of cells. Various cytokines can release ceramides, which then act as important intracellular signaling molecules. Considerable interest has focused on ceramide as a signaling molecule in apoptosis (programmed cell death) and in the development of muscle insulin resistance.

Cerebrospinal fluid (CSF)

  • CSF is the colorless bodily fluid occupying the subarachnoid space and the ventricular system around and inside the spinal cord and brain.

cGMP

  • cGMP stands for cyclic guanosine monophosphate. It is avery important intracellular signalling molecule in cells. Insmooth muscle, an increase in cGMP results invasodilation. The vasodilator effects of nitric oxide (NO)are mediated by cGMP.

Chemokines

  • Chemokines are small protein cytokines secreted by cells that induce chemotaxis (migration towards chemicals in the nearby environment) of neighbouring responsive cells.

Cholesterol (7 beta-Hydroxy)

  • 7β-Hydroxycholesterol is a cholesterol ester. Since freeradicals can produce 7β-hydroxycholesterol, the levels ofplasma 7β-hydroxycholesterol are sometimes used as amarker of free radical injury.

Cholesterol ester transfer protein (CETP)

  • Cholesterol ester transfer protein (CETP) facilitates reversecholesterol transport from high-density lipoprotein (HDL)to triacylglycerol-rich lipoproteins. High plasma levels ofCETP are correlated with low HDL cholesterol levels, astrong risk factor for coronary artery disease.

Chromatin

  • Chromatin is the DNA-containing chromosomal material ofthe nucleus.

Chromosomal “locus” and “focus”

  • The chromosomal “locus” refers to the specific location of a DNA sequence/gene on a chromosome, whereas the “focus” refers to the 3-dimensional architecture of mutually exclusive domains of a chromosome.

Chronic occlusion

  • Chronic occlusion usually refers to the sustained occlusionof a coronary blood vessel.

CoA dehydrogenase (3-Hydroxyacyl-)

  • 3-hydroxyacyl-CoA dehydrogenase is the third enzyme inthe intramitochondrial pathway that is involved in themetabolism of fatty acids (fatty acid b-oxidation). Recentinterest has focused on inhibition of fatty acid oxidation asa way to protect the ischemic heart.

Conjugated dienes in circulating low-density lipoproteins

  • Conjugated dienes are a product of free radical reactionwith lipids. The presence of conjugated dienes incirculating low-density lipoproteins is used as a marker ofoxidant stress by free radicals.

Connexin 43

  • Gap junction channels are essential for intercellularcommunication between cardiac cells. Among the mostabundant gap junction channel proteins is connexin 43.

CrCl level

  • CrCl is the abbreviation for creatinine clearance.Measurement of creatinine clearance rates is used toassess kidney function.

Creatine kinase-muscle/brain-type subunit (CK-mb)

  • CK-mb is the enzyme that catalyzes the conversion of creatine to phosphocreatine in an ATP-dependent manner, and is thus essential for restoring phosphocreatine levels, the primary energy reserve for buffering ATP levels in the cell. CK-mb is the isoform containing both a muscle and brain type sub-unit, and represents approximately 30% of total creatine kinase protein in the myocardium.

Creatine/phosphocreatine

  • Phosphocreatine is a chemical storage form of energy incells. In times of increased energy demand, the highenergy phosphate on phosphocreatine can be transferredto adenosine diphosphate (ADP) to form adenosinetriphosphate (ATP) and creatine. ATP is then used byenzymes in energy requiring cellular processes. In times oflow energy demand, the reverse reaction occurs, withcreatine kinase catalyzing the formation ofphosphocreatine and ADP from ATP and creatine. Acreatine and phosphocreatine shuttle system is importantin the transfer of high energy phosphates frommitochondria to the cytoplasm.

Cyclo-oxygenase

  • The cyclo-oxygenase enzymes are an important group ofenzymes involved in the metabolism of arachidonic acid toprostaglandins. Prostaglandins have diverse biologicalactions in the body.

Cyclosporin A

  • Cyclosporin A is an immunosuppressive agent that inhibits MPTP opening via binding to cyclophilin D.

Cytochrome c

  • Cytochrome c is a mitochondrial protein that has animportant electron-transport function in mitochondrialrespiration. Recently, cytochrome c release from themitochondria has been shown to be an important earlyevent in the apoptotic (programmed cell death) pathway.Release of cytochrome c from the mitochondria triggers aseries of events leading to cell death.

Cytochrome c oxidase

  • Cytochrome c oxidase is a mitochondrial enzyme that hasan important role in the electron transport function ofmitochondrial respiration. The oxidation of cytochrome cby cytochrome c oxidase is one of the steps that results inelectron transport via this pathway. The electron transportchain transfers electrons through a number of differentenzyme complexes which catalyze the pumping of protonsout of the mitochondrial matrix. These protons can thenpass back into the mitochondria via an enzyme called ATPsynthase. The downhill electrochemical gradient of thisprocess produces energy that results in the production ofATP from ADP. ATP is a form of chemical energy used inmost cellular processes requiring energy.

Cytochrome P-450 mono-oxygenases

  • Cytochrome P-450 mono-oxygenases play an important role insteroid metabolism and in drug clearance in the liver.

Cytokines

  • Cytokines refer to a group of compounds that are producedunder a variety of conditions, including the immuneresponse and inflammatory reactions. Tumor necrosisfactor-a and interleukin-1 are examples of two cytokines.

Cytoskeletal proteins

  • Cytoskeletal proteins are important structural proteins ofthe cell that have an important role in maintaining cellshape and structure.

Decanoic acid (18F-labeled 6-thia-hepta-)

  • 18F-labeled 6-thia-hepta-decanoic acid is an 18F-labeledfatty acid. It can be used to measure fatty acid metabolismin tissue, by following the myocardial fate of 18F withpositron emission tomography (PET) imaging. This tracerhas been used for measuring fatty acid metabolism in vivo,including the identification of defects in fatty acidmetabolism in subjects with medium- and short-chainfatty acid oxidation defects.

Dendritic cells

  • Dendritic cells are antigen-presenting cells that link the innate (ie, nonspecific) and adaptive (ie, specific) immune systems. Dendritic cells are important in initiating T-cell activation and responses.

Deoxyguanosine (8-OHdG)

  • 8-OH-deoxyguanosine (8-OHdG) is produced when DNA issubjected to free radical attack. Leukocyte DNA 8-OHdGlevels are sometimes used as a measure of free radicalinjury to DNA.

Desmin

  • Most cells contain microfilaments that are important inthe cytoskeleton of the cell. Desmin is a common proteinfound in these microfilaments.

Diabetic db/db mouse

  • The genetic leptin-resistant (db/db) mouse possesses amutation in the leptin-receptor, resulting in a defective leptinreceptor.This leptin-receptor deficiency induces ahyperglycemic-hyperinsulinemic endometabolic environmentthat results in the development of type 2 diabetes.

Diacylglycerol

  • Diacylglycerol (DAG) consists of two fatty acids attached to a glycerol backbone and is the preceding intermediate in the biosynthesis of TAG. The accumulation of DAG in skeletal muscle and the liver has been linked to the development of muscle and hepatic insulin resistance.

Dicer

  • Dicer is a large multidomain protein possessing RNase III activity that is involved in processing larger RNA precursors into smaller RNA species. Dicer is responsible for cleaving pre-microRNAs into mature microRNAs, and double-stranded RNAs into small interfering RNAs.

Dichloroacetate (DCA)

  • Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which is the enzyme responsible for phosphorylating and inactivating pyruvate dehydrogenase, the rate-limiting enzyme of glucose oxidation. DCA therefore activates pyruvate dehydrogenase and increases subsequent glucose oxidation rates.

Dimerize

  • Dimerize is a term to describe the combination of twoproteins or nucleic acid chains into one complex.

Dipeptidyl peptidase-4 (DPP-4)

  • DPP-4, also known as cluster of differentiation 26 (CD26), is a multifunctional enzyme best known for its biological activity to act as a protease that cleaves dipeptides from the N-terminus of proteins immediately following a position-2 proline or alanine amino acid. Because of its ability to cleave the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), DPP-4 inhibitors have been developed to prevent degradation of GIP and GLP-1 for the treatment of type 2 diabetes. Other biological functions of DPP-4 include an association with adenosine deaminase, cell-surface coreceptor activity involved in viral entry, and the regulation of signal transduction coupled to the control of migration and proliferation of cells.

Dipeptidyl peptidase-4 (DPP-4)

  • DPP-4, also known as cluster of differentiation 26 (CD26), is a multifunctional enzyme best known for its biological activity to act as a protease that cleaves dipeptides from the N-terminus of proteins immediately following a position-2 proline or alanine amino acid. Because of its ability to cleave the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), DPP-4 inhibitors have been developed to prevent degradation of GIP and GLP-1 for the treatment of type 2 diabetes. Other biological functions of DPP-4 include an association with adenosine deaminase, cell-surface coreceptor activity involved in viral entry, and the regulation of signal transduction coupled to the control of migration and proliferation of cells.

Dismutase

  • Dismutase (usually called superoxide dismutase) is anenzyme that converts superoxide radicals to hydrogenperoxide.

Disulfide bonds (RSSR)

  • A disulfide bond is a bond in proteins between two sulfurmolecules. Disulfide bonds are an important mechanismby which proteins maintain their three-dimensionalconfiguration. If the disulfide bond is broken (for instancedue to a reaction with a free radical), the function of theprotein can be compromised.

Dithiothreitol

  • Dithiothreitol is a strong thiol reductant. It preventssulfhydryl groups from being oxidized.

Drugs affecting testosterone

  • Drugs affecting testosterone are any medication/agent that influences circulating testosterone levels and includes antihypertensives, and agents such as statins (ie, atorvastatin and simvastatin) and spironolactone, which decrease testosterone levels, whereas the ovulation inducer clomiphene increases testosterone levels.

Dyslipidemia

  • Dyslipidemia is an abnormal amount of lipids (i.e., fatty acids and/or cholesterol) in the blood. In developed nations this is primarily an elevation in plasma lipids, often resulting from diet and lifestyle choices.

Ectonucleotide pyrophosphatase/phosphodiesterase 1

  • Ectonucleotide pyrophosphatase/phosphodiesterase is aplasma cell membrane glycoprotein that functions to releasenucleoside 5’-monophosphates from various nucleotides(such as ATP). There has been interest in the ectonucleotidepyrophosphatase/phosphodiesterase since a K121Qpolymorphism in the enzyme has been shown to be associatedwith obesity, glucose intolerance and insulin resistance.A number of variants of ectonucleotide pyrophosphatase/phosphodiesterase have now been identified to have a primaryrole in mediating insulin resistance and the development ofobesity and type 2 diabetes.

Edema

  • Edema is the excess extravasation into, and hence accumulation of fluid in, the interstitial/extracellular space.

Eicosapentanoic acid and docosahexanoic acid

  • Eicosapentanoic acid (EPA) and docosahexanoic acid(DHA) are polyunsaturated fatty acids that are found inabundance in fish oils. EPA and DHA are thought to beeffective in treating a number of disorders, many involvinginflammation. EPA and DHA can also reduce the level ofblood triglycerides in humans, which may reduce the riskof heart disease. Dietary consumption of EPA and DHAhave been demonstrated to reduced total mortality,cardiovascular mortality, and morbidity.

Electron transport chain

  • The electron transport chain encompasses a series of four inner mitochondrial membrane protein complexes that allow electron transfer between electron donors (i.e., NADH/FADH2) and electron acceptors such as O2. The transfer of electrons between these complexes causes the transfer of protons from inside the mitochondrial matrix outside into the mitochondrial inner membrane space, which drives an electrochemical proton gradient used to drive ATP synthesis in the process of oxidative phosphorylation.

Electron transport chain

  • This encompasses a series of five inner mitochondrial membrane protein complexes that allow electron transfer between electron donors (i.e., NADH/FADH2) and electron acceptors such as O2 (these four protein complexes themselves act as both electron acceptors and then subsequent electron donors as they pass electrons to the following complex). The transfer of electrons between these complexes causes the transfer of protons from inside the mitochondrial matrix outside into the mitochondrial inner membrane space, which drives an electrochemical proton gradient used to drive ATP synthesis in the process of oxidative phosphorylation.

Endothelial nitric oxide synthase

  • Nitric oxide synthase is the enzyme responsible forsynthesizing nitric oxide. Nitric oxide has receivedconsiderable research attention, since it is not only avasodilator but is also important in numerous otherprocesses, including apoptosis. Nitric oxide synthasepresent in endothelial cells is an important source of nitricoxide.

Endothelin-1

  • Endothelin-1 is small peptide produced in a variety oftissues including endothelial and vascular smooth-musclecells. It acts as a modulator of vasomotor tone, cellproliferation, and hormone production. It is a potentvasoconstrictor.

Endothelin-1

  • Endothelin-1 is a small peptide produced in a variety of tissues, including endothelial and vascular smooth muscle cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. It is a potent vasoconstrictor.

Endurance

  • Endurance is often used interchangeably with the term “stamina” and represents the ability of individuals to exert themselves and remain active over a duration of time. It may also include the individual’s ability to withstand and recover from the fatigue of exertion.

Episome

  • Episome refers to an extrachromosomal genetic element (eg, DNA) that is capable of replication when supplied with the necessary factors. Therefore, episomal expression vectors allow for gene transfer and subsequent transgene expression in the absence of chromosomal integration.

Epoxyeicosatrienoic acids

  • Epoxyeicosatrienoic acids (EETs), which are synthesizedfrom arachidonic acid by cytochrome P450 epoxygenases,function primarily as autocrine and paracrine effectors inthe cardiovascular system and kidney. The EETs havediverse actions, including somatostatin, insulin andglucagon release from the pancreas. They also modulateion transport and gene expression, producingvasorelaxation, as well as anti-inflammatory and profibrinolyticeffects.

Erectile dysfunction

  • Erectile dysfunction is a form of sexual dysfunction that involves an inability of the penis to maintain an erection during sexual activity. Erectile dysfunction is commonly treated with phosphodiesterase type 5 inhibitors such as sildenafil (Viagra), which prevent the breakdown of cyclic guanosine monophosphate and relaxes smooth muscle cells in the blood vessels supplying the corpus cavernosum of the penis.

Exenatide

  • Exanatide is the synthetic version of the GLP-1 receptor agonist hormone, exendin-4, and is currently used in the treatment of type 2 diabetes due to its ability to enhance glucose-stimulated insulin secretion.

Exosome

  • Exosomes are small vesicles derived from late endosomes. Exosomes participate in secreting damaged proteins and RNA from the cell.

F2-isoprostanes

  • Free radical peroxidation of lipids can produce F2-isoprostanes. As a result, the production of F2-isoprostanes has been used as a measure of oxidant stress.

Fatty acid binding protein (FABP)

  • Fatty acid binding protein is an abundant cytoplasmicprotein (especially cardiac cells) that binds fatty acids andfacilitates their transport to intracellular compartments.One of its functions is to transport fatty acids from the cellmembrane to the mitochondria.

Fatty acid synthase (FAS)

  • FAS is an important enzyme in the synthesis of fatty acids,primarily in liver cells. In eukaryotes, synthesis of fattyacids takes place on a large, multifunctional FAS enzymecomplex formed from a single polypeptide chain. MalonylCoA serves as a substrate for the synthesis of fatty acids.

Fatty acid translocase (FAT)

  • Fatty acid translocase (FAT) is a protein found in theplasma membrane of many cells and is thought to beinvolved in the transport of fatty acids across themembrane and into the cell. It has been suggested thatFAT is responsible for a significant portion of fatty aciduptake into the cardiac cell.

Fatty acids

  • Fatty acids are a group of molecules that consist of a carboxylic acid with hydrocarbon chains of varying lengths. Most naturally occurring fatty acids are synthesized from acetate, as such contain even numbers of carbon atoms, which can be saturated with hydrogen (i.e., the molecule is devoid of carbon-carbon double bonds), or unsaturated to varying degrees (i.e., the molecule contains carbon-carbon double bonds). Fatty acids represent an important energy substrate for cardiac energy metabolism.

FGF-2 (fibroblast growth factor-2)

  • FGF-2 exists as low molecular weight (18 kDa) and high molecular weight isoforms (20-34 kDA). It belongs to a large family (FGF-1-FGF23) of highly conserved heparin binding growth factors that act by binding to and activating cell surface receptors (FGFR1-FGFR4) possessing intrinsic tyrosine kinase activity.

Fibroblast growth factors (FGFs)

  • FGFs are secreted glycoproteins, which are localized to the extracellular matrix by heparin sulfate proteoglycans. The activity of various heparinases, proteases, and FGF-binding proteins will release FGFs from the extracellular matrix, and then free FGFs can activate cell surface FGF receptors. FGF2 is the most characterized FGF and important paracrine factor involved in the development of cardiac hypertrophy.

Fibroblasts

  • Fibroblasts are immature fiber-producing cells capable ofdifferentiating into chondroblasts, collagenoblasts orosteoblasts.

Flip-flop mechanism

  • This term describes the movement of fatty acid molecules across the phospholipid bilayer that comprises the cell membrane. Flip-flop involves reorientation of a fatty acid molecule such that the polar carboxyl moiety originally interacting with the lipid-aqueous interface of the external leaflet and the extracellular space subsequently interacts with the lipid-aqueous interface of the internal leaflet and cytosolic space. Following this reorientation, the fatty acid molecule can dissociate from the inner leaflet of the phospholipid bilayer and completely enter the aqueous cyotosolic compartment.

Follicle-stimulating hormone

  • Follicle-stimulating hormone (FSH) is a heterodimeric glycoprotein consisting of α and β subunits, and has a molecular weight of 28-29 kDa. FSH is synthesized and released by gonadotrophs in the anterior pituitary in response to stimulation by gonadotropin-releasing hormone, itself released from hypothalamic neurons into the capillary networks of the hypothalamic median eminence and lower infundibular trunk. In males, FSH stimulates Sertoli cells in the testis, which are critical to germ-cell development. In females, it acts on the ovaries to stimulate follicle development and is the main hormone controlling estrogen secretion.

Fractional Flow Reserve (FFR)

  • FFR is an invasive measurement, defined as the ratio of maximum blood flow in a stenotic epicardial coronary artery, relative to maximum theoretical blood flow in the same artery in the absence of a stenotic lesion. The ratio of the two flows is expressed as the ratio of two driving pressures for coronary flow, Pd and Pa. Pd represents pressure across the stenotic lesion, whereas, Pa represents aortic pressure, both measured at maximum coronary flow. FFR identifies hemodynamically significant coronary stenosis that predisposes to inducible ischemia. FFR functions as a decision making tool for revascularization.

Framingham Heart Study

  • The Framingham Heart Study was initiated in 1948 as a joint effort between the National Heart Institute (now the National Heart Lung and Blood Institute) and Boston College and is now the longest running prospective cohort study in the United States. The objective of the study was to identify risk factors for the development of cardiovascular disease over time in participants who had not yet developed cardiovascular disease or suffered myocardial infarction or stroke. The first generation of participants was enrolled in Framingham, Massachusetts in 1948; a second generation, in 1971; and a third generation, in 2002 and 2003. The Framingham Heart Study has contributed to the understanding of overall and cardiovascular mortality in the setting of various pathologies, including obesity, diabetes, and metabolic syndrome.

Free fatty acids (FFAs)

  • Acid moieties found in the circulation bound to albumin, or derived from triacylglycerol contained in chylomicrons or very-low density lipoprotein. Following cellular uptake, free fatty acids are activated via esterification to coenzyme A, and can be metabolized via mitochondrial fatty acid β-oxidation to generate reducing equivalents (e.g., nicotinamide adenine dinucleotide [NADH]) for the electron transport chain and oxidative phosphorylation.

Free radicals

  • Free radicals are usually either oxygen or hydroxyl groupsthat have an unpaired electron. These free radicals areunstable and react with lipids, proteins, or DNA and RNA.This can result in tissue damage.

G-proteins

  • G-proteins refer to a group of guanylate triphosphate (GTP)binding proteins that are crucial in linking numerous typesof receptor to their subcellular signalling pathways. Anexample of this is the b-adrenergic receptor, which iscoupled to adenylate cyclase via a G-protein. Receptorsthat are coupled to the G-protein family are called Gproteincoupled receptors.

Gadolinium

  • Gadolinium is a rare earth metal that can be used as a research tool for applications such as magnetic resonance imaging (MRI). It can be used as an MRI contrast agent because, as a paramagnetic ion, it moves differently within a magnetic field. Gadolinium can also be used in ion channel electrophysiology experiments to block sodium channel leaks, as well as to stretch activated ion channels.

Galactosidase (alpha-)

  • Galactosidases are enzymes that metabolize saccharides.One of these, a-galactosidase, acts on the a-galactosidiclinkage of the globotriaosylceramide (Gb3) receptor, atumor-associated carbohydrate antigen. In response totoxins, such as Shiga toxin, a-galactosidase activity can bedecreased. This increases Gb3 receptor content,increasing a cytotoxic response.

Gallic acid

  • Gallic acid is a tannin that is thought to exert antioxidantactivity. It has been proposed that the presence of gallicacid in red wine has beneficial antioxidant effects.

GAMT knock out mice

  • Creatine is an important molecule involved in energystorage and in transmission of phosphatebound energysubstrates. One of the creatine synthetic enzymes isS-adenosyl-L-methionine:Nguanidinoacetatemethyltransferase (GAMT). GAMT knockout mice lackGAMT, and therefore have a defect in creatine synthesis.They are therefore useful in looking at the role of creatinedeficiency in energy homeostasis.

Genotype/Phenotype

  • Genotype represents the inherited instructions that an organism carries within its genetic code, whereas phenotype represents the observable characteristics of that organism, which is often determined via the interaction between that organism’s genotype with the environment.

Geranylgeranyl-pyrophosphate

  • Geranylgeranyl pyrophosphate (GGPP) is an isoprenoid that is aprecursor for numerous molecules essential for cellular function.GGPP also acts as a substrate in isoprenylation reactions.GGPP is produced from farnesyl-PP, which is produced fromgeranyl-PP, an intermediate in the cholesterol synthetic pathway.Inhibition of GGPP production, using a geranylgernayltransferase inhibitor can inhibit vascular smooth muscleproliferation. A similar effect can be observed by HMG-CoAreductase inhibition, which inhibits the production ofmevalonate, which eventually can go on to produce geranyl-PP.

Ghrelin

  • Ghrelin is a peptide hormone secreted in the gastrointestinal tract via ghrelin cells and is commonly referred to as the “hunger hormone” since its plasma levels increase in the preprandial state and decrease in the postprandial state, suggesting that ghrelin has a physiological role in meal initiation.

Global longitudinal strain (GLS)

  • Global longitudinal strain (GLS) is a new technique for detecting, quantifying, and evaluating subtle disturbances/ deteriorations in left ventricular systolic function via use of speckle-tracking echocardiography.

Globotriaosylceramide (Gb3)

  • Globotriaosylceramide (Gb3) is a membranous lipidic receptor.Cytokines and binding of toxins, such as Shiga toxin andverotoxin, increase Gb3 expression. This can lead to the importof peptides and the initiation of cell toxicity and injury.

Glucagon

  • Glucagon is the principal secretory product of α-cells of pancreatic islets. Glucagon is a 29–amino-acidpeptide hormone derived from proglucagon via the action of prohormone convertase 2. The primary endocrine effects of glucagon are to increase hepatic glucose production by stimulating both hepatic glycogenolysis and gluconeogenesis to counter hypoglycemia.

Glucagon

  • Glucagon is the principal secretory product of β-cells of pancreatic islets. Glucagon is a 29-amino-acidpeptide hormone derived from proglucagon via the action of prohormone convertase 2. The primary endocrine effects of glucagon are to increase hepatic glucose production by stimulating both hepatic glycogenolysis and gluconeogenesis to counter hypoglycemia.

Glucagon-like peptide-1 (GLP-1)

  • GLP-1 is an incretin hormone synthesized and secreted from intestinal L cells. GLP-1 is derived from proglucagon via the action of prohormone convertase 1. Biologically active GLP-1 is generated from GLP-1(1-37) as either GLP-1(7-37) or GLP-1(7-36) amide, which represents the majority of biologically active GLP-1 in human plasma. GLP-1 exerts a variety of effects relevant to the regulation of glucose homeostasis, including enhancing glucose-stimulated insulin secretion, while inhibiting glucagon secretion. In addition, GLP-1 has been demonstrated to promote β-cell proliferation, inhibit β-cell apoptosis, decrease the rate of gastric emptying, and decrease food intake.

Glucagon-like peptide-1 (GLP-1)

  • GLP-1 is an incretin hormone synthesized and secreted from intestinal L cells. GLP-1 is derived from proglucagon via the action of prohormone convertase 1. Biologically active GLP-1 is generated from GLP-1(1-37) as either GLP-1(7-37) or GLP-1(7-36) amide, which represents the majority of biologically active GLP-1 in human plasma. GLP-1 exerts a variety of effects relevant to the regulation of glucose homeostasis, including enhancing glucose-stimulated insulin secretion, while inhibiting glucagon secretion. In addition, GLP-1 has been demonstrated to promote β-cell proliferation, inhibit β-cell apoptosis, decrease the rate of gastric emptying, and decrease food intake.

Glucocorticoids

  • Glucocorticoids are steroids produced by the adrenal gland thathave diverse actions on the body, including control of glucosemetabolism, and control gene expression. Glucocorticoidsregulate the transcription of a large number of genes, includinga number of gluconeogenic genes in the liver.

GLUT-1

  • GLUT-1 is a protein that transports glucose across cellmembranes. GLUT-1 primarily resided in the plasmamembrane, and unlike GLUT-4 it is not responsive to insulin.

GLUT-4

  • Glucose transporter- 4 (GLUT-4) is a protein that transports glucose across cell membranes. In insulin-responsive tissues (such as the heart), insulin will cause GLUT-4 to be translocated from inside the cell to the plasma membrane, thereby stimulating glucose uptake.

Glutathione

  • Glutathione is an amino acid that acts as a substrate forglutathione peroxidase. Increasing glutathione levels are thoughtto increase the antioxidant actions of glutathione peroxidase.

Glutathione peroxidase

  • Glutathione peroxidase is a peroxidase found in cells that helpsto prevent lipid peroxidation of the cell membrane. Thefunction of glutathione peroxidase is to reduce lipidhydroperoxides to their corresponding alcohols and to reducefree hydrogen peroxide to water.

Glycated hemoglobin

  • Glycated hemoglobin (HbA1c) forms from the nonenzymatic coupling of glucose to the major component of adult hemoglobin (ie, HbA α2β2). Glucose, via a complex series of reactions, is coupled to specific valine residues of HbA β chains. HbA1c levels at a threshold of 6.5% can be used as a diagnostic test indicative of diabetes. HbA1c levels are reflective of average glycemic control over a period of 2 to 3 months before testing/analysis.

Glyceraldehyde 3-phosphate (GA3PDH)

  • Glyceraldehyde 3-phosphate (GA3PDH) is a key enzyme ofglycolysis. During myocardial ischemia, GA3PDH can becomerate-limiting for glycolysis. GA3PDH mRNA expression levelsare often used as a control in many Northern blot experimentsin order to ensure that equal amounts of mRNA have beenloaded on the gel.

Glycogen synthase kinase 3 (GSK3)

  • GSK3 is an unusual protein serine/threonine kinase that, as thename implies phosphorylates glycogen synthase. The twomammalian isoforms, GSK-3a and b, play largely overlappingroles and have been implicated in a variety of human pathologies,including type 2 diabetes, Alzheimer's disease, bipolar disorderand cancer. Inhibition of ccglycogen synthase kinase-3 has beenshown to prevent caspase-dependent apoptosis.

Glycolysis

  • Glycolysis is the series of biochemical reactions occurring in the cytosolic compartment that converts a glucose molecule into two molecules of pyruvate. In the presence of oxygen (i.e., the aerobic setting), pyruvate is transported into the mitochondria, and undergoes oxidative decarboxylation yielding acetyl-CoA. In the absence of oxygen (i.e., the anaerobic setting), pyruvate is reduced to lactate by the enzyme lactate dehydrogenase, which generates NAD+ required to maintain flux through glycolysis.

Glycophosphatidylinositol-linked lipoprotein lipase

  • One type of post-translational modification of protein involvesthe addition of a glycophosphatidylinositol (GPI) anchor thatfacilitates anchoring of proteins to cell membrane. Aglycophosphatidylinositol-linkage on lipoprotein lipase is oneway of linking lipoprotein lipase to the cell membrane.

Glycosphingolipid metabolism

  • Sphingolipids are a type of phospholipid. Glycosphingolipidsare sphingolipids that are glycosylated. Globotriaosylceramideis an example of a glycosphingolipid.

Glycosylation end products

  • Glycosylation is the process of adding oligosaccharide moietiesto proteins or other molecules. In diabetes, chronically highglucose levels will increase the level of protein glycosylation.Therefore, by measuring glycosylation end products, the longerterm degree of glucose control can be determined.

Gpx1

  • Gpx1 is an abbreviation for glutathione peroxidase.

Growth factors

  • Growth factors are primarily proteins or steroid hormones that can stimulate cellular proliferation, growth, and/or differentiation. They are usually essential signalling molecules involved in the differentiation and maturation of cells (ie. preadipocyte to adipocyte).

Guanylate cyclase

  • Guanylate cyclase is an enzyme that catalyzes theformation of cGMP from guanosine triphosphate.Guanylate cyclase is a target of nitric oxide (NO), and isprimarily responsible for NO mediated vasodilation.

HbA1c

  • Glycated hemoglobin (HbA1c) forms from the nonenzymatic coupling of glucose to the major component of adult hemoglobin (ie, HbA α2β2). Glucose, via a complex series of reactions, is coupled to specific valine residues of HbA β chains. HbA1c levels at a threshold of 6.5% can be used as a diagnostic test indicative of diabetes. HbA1c levels are reflective of average glycemic control over a period of 2 to 3 months before testing/analysis.

Heart failure

  • The inability of the heart to pump enough blood to meet the body's demand. In heart failure, the organs and other tissues do not receive enough oxygen and nutrients to function properly. Common contributing factors in the inability of the heart to adequately function include hypertension and ischemic heart disease.

Heart failure with midrange ejection fraction (HFmrEF)

  • Heart failure with midrange ejection fraction (HFmrEF) is a new category of heart failure defined as heart failure with an ejection fraction between 40% and 49%. This new class of heart failure is meant to apply to patients in a “gray zone,” where the benefits of therapies on morbidity and mortality have not been conclusively proven as they have been for patients with HFrEF.

Heart failure with midrange ejection fraction

  • Heart failure with midrange ejection fraction (HFmrEF) is a new category of heart failure defined as heart failure with an ejection fraction between 40% and 49%. This new class of heart failure is meant to apply to patients in a “gray zone,” where the benefits of therapies on morbidity and mortality have not been conclusively proven as they have been for patients with HFrEF.

Heart failure with reduced ejection fraction (HFrEF)

  • Heart failure with reduced ejection fraction (HFrEF) is usually defined as heart failure with an ejection fraction lower than 40% and is characterized by systolic dysfunction. It is primarily accompanied by eccentric remodeling and a decreased left ventricular wall thickness. Approximately 50% of all heart failure cases are classified as HFrEF.

Heat shock proteins (HSPs)

  • Heat shock proteins are cytoprotective, molecular chaperone proteins, belonging to five families based on molecular weight (kDa)—HSP100, HSP90, HSP70, HSP60, and small HSPs (12-43 kDa).

Hemoproteins

  • Hemoproteins are proteins that contain a heme molecule,which is an iron-containing protophorphyrin. CytochromeP-450 and hemoglobin are two examples of hemoproteins.

Heptadecanoic acid (IHDA)

  • Heptadecanoic is a 16-carbon fatty acid that can beradiolabeled and used as a tracer for fatty acid uptake intothe heart. One of the radiolabels that can be attached toheptadecanoic acid is a 123I group, which produces 123Iheptadecanoicacid (IHDA). A gamma camera can then beused to measure 123I-heptadecanoic acid uptake into theheart. This approach is used to assess fatty acidmetabolism in the heart.

Heterodimeric

  • The term heterodimeric refers to two different proteinsthat combine to form a complex.

Hexokinase

  • Hexokinase is an important enzyme that phosphorylatesglucose to glucose-6-P in the cytoplasm of cells. Thisallows glucose to be further metabolized. The glucose-6-Pcan be used as a substrate for glycolysis, a substrate forglycogen synthesis, or as a substrate for the pentosephosphate pathway. However, all of these pathways requirethat hexokinase first phosphorylate glucose.

Hibernating myocardium

  • This state, in which segments of myocardium are viable but exhibit abnormalities in contractile function, is often observed in chronic ischemia.

HOMA-IR

  • Homeostasis model assessment of insulin resistance (HOMA-IR) is a clinically utilized index of insulin resistance calculated as the product of fasting plasma glucose concentration (expressed in mmol/L) and fasting plasma insulin concentration (expressed in µU/mL) normalized to a constant, 22.5. The constant, itself, reflects the product of normal fasting plasma glucose (ie, 4.5 mmol/L) and normal fasting plasma insulin (ie, 5 µU/mL).

Hormones

  • Hormones are chemical substances classically released from ductless cells into the circulation (can also be released into the interstitial fluid), and elicit effects at target cells. These effects may occur at distant target cells, nearby cells (paracrine), or the same cell (autocrine). Hormones regulate and coordinate biological functions via cell-to-cell communication and thus contribute to the maintenance of homeostasis.

Human menopausal gonadotropin (hMG)-coenzyme A reductase inhibitors

  • Human menopausal gonadotropin (hMG)-coenzyme Areductase is important in the production of gonadal steroidhormones. There has been concern that the commonlyused hMG reductase inhibitors used to lower cholesterolmay also inhibit gonadotropincoenzyme.A reductase, therefore altering gonadal steroid hormoneproduction.

Hydrobiopterin

  • Tetra-hydrobiopterin is produced by the reduction ofdihydrobiopterin, catalyzed by the enzyme, dihydrofolatereductase. Tetra-hydrobiopterin is an essential cofactor fornitric oxide (NO) formation.

Hydrogen peroxide

  • Hydrogen peroxide is an intermediate between two freeradicals. Superoxide radicals can be acted upon bysuperoxide dismutase to produce hydrogen peroxide.However, if hydrogen peroxide is not subsequentlyremoved from the cell (usually by catalase), anonenzymatic reaction can occur in which highly reactivehydroxyl radicals are produced.

Hydroperoxides

  • Hydroperoxides contain the O–O–H– unit. Hydrogen peroxideis therefore also an example of a hydroperoxide. Anotherhydroperoxide, lipid hydroperoxides, are also a marker of freeradical injury. Free oxygen radicals can react with membranelipids to form lipid hydroperoxides, a destructive processknown as lipid peroxidation. Lipid peroxidation leads tooxidative injury of biologic membranes in vivo.

Hydroxyl

  • A hydroxyl free radical is a hydroxyl group with an unpairedelectron. It is a highly reactive free radical that can causeserious damage to a cell by reacting with lipids, proteins,or DNA.

Hyperemia

  • Hyperemia refers to an increase in blood flow to a region of the body. Active hyperemia occurs in response to an increase in metabolic/energetic demand whereas, reactive hyperemia occurs transiently, following brief ischemia.

Hyperinsulinemic-euglycemic clamp

  • During a hyperinsulinemic-euglycemic clamp, high insulinlevels are infused into a patient (or animal) and glucose issubsequently infused at a rate which maintains normalblood glucose levels. This procedure is used to determinethe insulin sensitivity of the muscle. The more glucoseinfused under conditions of hyperinsulinemia the moreinsulin-sensitive is the muscle.

Hypertrophy

  • In human physiology, hypertrophy is the increase in the volume/size of an organ or tissue due to the enlargement of the individual cells making up that organ. For example, exercise often induces hypertrophy of the heart due to stretching of ventricular myocytes in order to pump a larger volume of blood.

Hypoxia

  • Hypoxia is a pathophysiological state characterized by decreased oxygen content in inspired air and/or blood, which can decrease oxygen delivery to metabolising tissues of the body despite adequate perfusion/blood flow.

Hypoxia-inducible factor-1alpha (HIF-1-α)

  • Hypoxia-inducible factor-1α (HIF-1-α) is a transcriptionalfactor that is activated by stresses such as hypoxia. HIF-1α then modifies the transcription of a number of genes,including glycolytic enzymes.

I-123 β–methyl-phenyl pentadecanoic acid (BMIPPA)

  • I-123 β–methyl-phenyl pentadecanoic acid (BMIPPA) is aradiolabeled fatty acid analog that can be used as animaging agent to assess fatty acid uptake into tissues. It isoften used to determine whether fatty acid uptake isaltered in the hearts of patients. This is established byusing a gamma-camera to determine the amount ofBMIPPA taken up by the heart.

If current

  • If is the abbreviation for a current that activelyhyperpolarizes cells. The “f” stands for “funny” becausethis unusual current hyperpolarizes cells. If current isprimarily present in the autonomic tissue of the heart (i.esinoatrial and AV node). It contributes to the phase 4depolarization of the cell.

If current

  • The funny current (If), also referred to as a pacemaker current, is a hyperpolarization-activated inward current of mixed ionic nature (Na+, K+) that contributes to pacemaker activity in sinoatrial node cells (also atrioventricular node cells, and Purkinje fibers). The pore-forming subunits of the If channel are formed by members of the hyperpolarization-activated cyclic nucleotide–gated gene family (HCN1-HCN4). As such, If is responsive to changes in intracellular cyclic adenosine monophosphate (cAMP) levels in response to, for example, the activation of β adrenoceptors (increased cAMP) or M2 muscarinic receptors (decreased cAMP), and thus contributes to the basic physiological mechanisms mediating the effects of the autonomic nervous system on heart rate.

Immunoabsorption (affinity chromatography)

  • A chromatographic method for the purification of a specific molecule(s) from a complex mixture(s) based on the highly specific biological interaction between two molecules (i.e., antibody and antigen). The interaction is usually reversible, and purification is achieved by immobilizing one of the molecules (affinity ligand) onto a solid matrix, thereby creating a stationary phase, while the target ligand is in a mobile phase as part of a complex mixture. Capture of the target molecule is typically followed by washing and elution, which results in the recovery of a purified molecular species.

Incretin

  • Incretin refers to gastrointestinal peptide hormones released by enteroendocrine cells of the intestinal mucosa in response to the ingestion of food (or oral glucose load). The two major incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins enhance glucosestimulated insulin secretion, and thus are important regulators of glucose homeostasis. In addition, a variety of extraglycemic effects of incretins have been documented, including a slowing of gastric emptying, promotion of satiety, and reductions in food intake.

Incretin

  • Incretin refers to gastrointestinal peptide hormones released by enteroendocrine cells of the intestinal mucosa in response to the ingestion of food (or oral glucose load). The two major incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins enhance glucosestimulated insulin secretion, and thus are important regulators of glucose homeostasis. In addition, a variety of extraglycemic effects of incretins have been documented, including a slowing of gastric emptying, promotion of satiety, and reductions in food intake.

Incretin

  • Incretin refers to gastrointestinal peptide hormones released by enteroendocrine cells of the intestinal mucosa in response to the ingestion of food (or oral glucose load). The two major incretins are glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins enhance glucose-stimulated insulin secretion and, thus, are important regulators of glucose homeostasis. In addition, a variety of extraglycemic effects of incretins have been documented, including a slowing of gastric emptying, promotion of satiety, and reductions in food intake.

Inducible nitric oxide synthase (iNOS)<

  • Nitric oxide synthase (NOS) is the enzyme responsible forsynthesizing nitric oxide (NO). NO has receivedconsiderable research attention, since it is not only avasodilator but is also important in numerous otherprocesses, including apoptosis. Inducible NOS (iNOS) isan isoform of NOS that can be dramatically induced undera variety of conditions. One example of this is the dramaticexpression of iNOS in muscle following sepsis.

Inflammasome

  • The inflammasome represents large intracellular protein complexes/platforms participating in the innate immune response that mediate the activation and recruitment of inflammatory cells to the affected site in the body by the release of proinflammatory mediators.

Inflammation

  • Inflammation is the normal response to stimuli including physical (eg, physical injury) and chemical stresses (eg, foreign substances in the body) that elicit cellular damage. The inflammatory process is characterized by distinct phases including initiation, the recruitment of cellular mediators and the release of inflammatory mediators, and contributes to tissue repair following injury. An inappropriate and/or prolonged inflammatory response that is not selflimiting can contribute to cellular damage.

Inorganic phosphate

  • Inorganic phosphate (HPO42-) functions as a substrate, along with ADP to form ATP via the process of mitochondrial oxidative phosphorylation. It is a product when ATP is hydrolyzed to ADP to provide cellular energy for various processes including active transport, anabolic metabolism, and muscle contraction.

Insulin

  • Insulin is a pancreatic peptide hormone secreted from β cells of the islets of Langerhans in the postabsorptive state. Its major metabolic effects are anabolic in nature, exemplified by the ability of insulin to: increase glucose and amino acid uptake as well as glycogen and protein synthesis in muscle increase glucose uptake and triacylglycerol synthesis in adipose tissue and increase glucose uptake, glycogen and triacylglycerol synthesis in the liver.

Insulin

  • Insulin is a pancreatic peptide hormone secreted from β-cells of the islets of Langerhans in the postabsorptive state. Its major metabolic effects are anabolic in nature, exemplified by the ability of insulin to do the following: increase glucose and amino acid uptake, as well as glycogen and protein synthesis, in muscle; increase glucose uptake and triacylglycerol synthesis in adipose tissue; and increase glucose uptake, glycogen, and triacylglycerol synthesis in the liver.

Insulin receptor substrate (IRS)-1

  • Insulin receptor substrate (IRS)-1 is a key protein in theinsulin-signaling pathway. Binding of insulin to thereceptor results in activation of IRS-1. IRS-1 then altersthe activity of a number of downstream signaling pathwaysto mediate the diverse effects of insulin.

Insulin resistance/insulin sensitivity

  • Insulin resistance is characterized by the failure of insulin to mediate its metabolic actions in tissues that express the insulin receptor. As the primary role of insulin is to stimulate glucose uptake into insulin sensitive tissues (such as skeletal muscle, heart, and adipose tissue), insulin resistance often results in hyperglycemia as insulin fails to stimulate glucose uptake into these tissues. Insulin sensitivity represents how effectively insulin is able to stimulate glucose uptake into its target tissues.

Insulin-like growth factors (IGFs)

  • IGFs (IGF-1 and IGF-2) share sequence similarity with insulin. IGF-1 is an important mediator of the effects of growth hormone (GH). Secretion of GH increases IGF-1 secretion from the liver and local tissues, which, in turn, stimulates systemic body growth. In the heart, IGF-1 is an important regulator of physiological growth/physiological hypertrophy. Furthermore, IGF-1 may be implicated in heart failure where its circulating levels are decreased.

Interleukin (IL)-1

  • Interleukin (IL)-1 is a proinflammatory cytokine which isinvolved in many immune responses, includingphysiological stress reactions. IL-1 has a diverse numberof biological actions, part of which occur through ceramidesignaling.

Interleukin-6 (IL-6)

  • Interleukin-6 (IL-6) is a proinflammatory cytokine involved inmany immune responses, including physiological stressreactions. IL-6 is also involved in several diseases, includinglymphoid malignancies. This cytokine binds to soluble IL-6receptor circulating in blood, leading to signal transduction. Asignificant correlation between circulating IL-6 level andinsulin sensitivity has recently been found in humans.

IP3-sensitive

  • IP3 is an important intracellular signaling molecule that isreleased from phosphatidylinositol present in thephospholipid cell membrane. IP3-sensitive refers to anysignalling pathway that involves IP3.

Ischemic postconditioning

  • An endogenous cardioprotective phenomenon in which brief cycles of ischemia and reperfusion applied at the onset of reperfusion render the myocardium tolerant of acute myocardial reperfusion injury.

Ischemic preconditioning

  • An endogenous cardioprotective phenomenon in which brief cycles of nonlethal ischemia and reperfusion render the myocardium tolerant of a subsequent, otherwise lethal, episode of acute ischemia/reperfusion injury.

K ATP channels

  • KATP channels are a type of potassium channel inhibitedby adenosine triphosphate. In the heart they are presenteither in the sarcolemmal membrane or in themitochondrial membrane. There is considerable researchinterest in activating KATP channels as an approach toprotecting the ischemic heart.

KAT (3-)

  • 3-KAT is the abbreviation for 3-ketoacyl-CoA thiolase

KAT inhibitor (3-)

  • 3-KAT is the abbreviation for 3-ketoacyl-CoA thiolase.3-KAT is the last enzyme in the intramitochondrialpathway that is involved in the metabolism of fatty acids(fatty acid β-oxidation). 3-KAT inhibitors, such astrimetazidine, inhibit the activity of this enzyme, therebyinhibiting fatty acid oxidation. Recent interest has focusedon 3-KAT inhibitors as a novel therapeutic approach toprotecting the ischemic heart.

KAT inhibitor (3-Ketoacyl-CoA-thiolase)

  • 3-Ketoacyl-CoA-thiolase (3-KAT) is the last enzyme in theintramitochondrial pathway that is involved in themetabolism of fatty acids (fatty acid β-oxidation). 3-KATinhibitors, such as trimetazidine, inhibit the activity of thisenzyme, thereby inhibiting fatty acid oxidation. Recentinterest has focused on 3-KAT inhibitors as a noveltherapeutic approach to protecting the ischemic heart.

Ketones

  • Ketones are a group of molecules than consist a carbonyl group (C=0) bonded to two carbon atoms. In most mammals ketones are formed in the liver from a reaction initiated by the enzymatic condensation of 2 molecules of acetyl-CoA. Ketones (e.g., acetoacetate) are transported in the plasma to extrahepatic tissues where they can be oxidized in the tricarboxylic acid cycle. Ketone bodies are overproduced during starvation, and in the setting of diabetes.

Kinase

  • A kinase is an enzyme that phosphorylates (i.e. adds aphosphate group) to other proteins and/or itself. Kinasesare very important enzymes involved in numerous cellsignalling processes.

Kinase (6-Phosphofructo-1-)

  • 6-phosphofructo-1-kinase (PFK-1) is an enzyme thatconverts fructose 6-phosphate to fructose 1,6-bisphosphate. PFK-1 is the rate-limiting enzyme ofglycolysis. As a result, regulation of PFK-1 is an importantmechanism by which glycolysis is regulated.

Kinase (6-phosphofructo-2-) PFK-2

  • PFK-2 is an enzyme that converts fructose 6-phosphate tofructose 2,6-bisphosphate. Fructose 2,6-bisphosphate is apotent stimulator of 6-phosphofructo-1-kinase (PFK-1),the rate-limiting enzyme of glycolysis. As a result,increasing fructose 2,6-biphosphate is an importantmechanism by which glycolysis is regulated.

L-arginine

  • L-arginine is an amino acid. An important function of Larginineis as a substrate for nitric oxide synthase, whichproduces nitric oxide (NO). NO is a potent vasodilator ofsmooth muscle.

Lamins (A-Type )

  • A-Type lamins are intermediate filament proteins thatbelong to the lamina, a ubiquitous nuclear network.Naturally occurring mutations in these proteins have beenshown to be responsible for several distinct diseases thatdisplay skeletal and/or cardiac muscle or peripheral nerveinvolvement.

Lapatinib

  • Lapatinib is a dual tyrosine kinase inhibitor that inhibits the HER2 receptor and is given orally in the treatment of solid tumors such as breast cancer. It has recently been approved as a front -line therapy for triple positive breast cancer.

Leptin

  • Leptin is a peptide hormone synthesized by adipocytes that plays a key role in the regulation of appetite and energy expenditure. This can occur through direct actions of leptin on the hypothalamus or via direct actions of leptin on peripheral lipid and glucose metabolism.

Leptin

  • Leptin is a peptide hormone synthesized by adipocytes and plays a key role in the regulation of appetite and energy expenditure. This can occur through direct actions of leptin on the hypothalamus or on peripheral lipid and glucose metabolism.

Leukotriene β

  • Leukotriene β is an eicosanoid that is synthesized fromarachidonic acid by the 5-lipoxygenase pathway. Leukotrines are involved in the inflammatory process, aswell as in vasoconstriction and vascular permeability.

Ligands

  • A ligand is term used to identify any molecule that bindsto another molecule. Examples of ligands includehormones, peptides, or other molecules that bind toreceptors or enzymes. For example, norepinephrine is aligand for the â-receptor, and fatty acids are ligands forperoxisome proliferator-activated receptors.

Lipid hydroperoxides (LOOH)

  • Lipid hydroperoxides (LOOH) are produced when freeradicals react with lipids. The levels of LOOH are oftenused as a measure of the amount of free radicalproduction or injury.

Lipid kinase termed PI3-kinase (phosphatidylinositol 3-kinase, PI3-K)

  • PI3-K is an intracellular kinase involved in a number ofimportant cellular pathways, including glucosemetabolism. PI3-K produces PtdIns(3,4,5)-P3, which ispart a signalling cascade initiated by a number of differenthormones, including insulin.

Lipid peroxidation

  • Lipid peroxidation is the term used to describe thereaction of free radicals with lipids.

Lipid peroxyl radicals

  • Reaction of free radicals with lipids produces lipid peroxylradicals. This is an unstable intermediate that then formsa more stable lipid hydroperoxide.

Lipin

  • Lipin is the product of the gene that is mutated in fattyliver dystrophy. Mice with this mutation exhibit severalphenotypic abnormalities, including hyperlipidemia,defects in adipocyte differentiation, impaired glucosetolerance, and slow growth.

Lipogenesis

  • Lipogenesis is a term describing the synthesis of lipids. Itoccurs primarily in the liver and adipocytes.

Lipoprotein lipase

  • Lipoprotein lipase (LPL) is an enzyme that cleaves fatty acids from TAG contained within lipoproteins.

Lipoxygenase

  • The lipoxygenase pathway comprises an important groupof enzymes involved in the metabolism of arachidonic acidto leukotrienes. Leukotrienes have diverse biologicalactions in the body.

Liver X receptors (LXRs)

  • Liver X receptors (LXRs) alpha and beta are responsible for thetranscriptional regulation of a number of genes involved incholesterol efflux from cells. LXRs limit cholesterolaccumulation by regulating expression of genes involved incholesterol efflux and storage. As a result, pharmacologicalactivation of LXRs may be a molecular target for the treatmentof cardiovascular disease.

Lixisenatide

  • Lixisenatide is a 44–amino-acid peptide developed by Sanofi-Aventis under the trade name Lyxumia. It is a short-acting glucagon-like peptide-1 (GLP-1) receptor agonist, administered via once-daily subcutaneous injection, and used in the treatment of type 2 diabetes. The therapeutic effects of lixisenatide (and GLP-1 receptor agonists as a drug class) include the stimulation of insulin secretion and glucose-lowering efficacy, slowing of gastric emptying, and the promotion of weight loss.

Lixisenatide

  • Lixisenatide is a 44-amino-acid peptide developed by Sanofi-Aventis under the trade name Lyxumia. It is a short-acting glucagon-like peptide-1 (GLP-1) receptor agonist, administered via once-daily subcutaneous injection, and used in the treatment of type 2 diabetes. The therapeutic effects of lixisenatide (and GLP-1 receptor agonists as a drug class) include the stimulation of insulin secretion and glucose-lowering efficacy, slowing of gastric emptying, and the promotion of weight loss.

Long-chain 3-ketoacyl coenzyme A thiolase

  • 3-ketoacyl-CoA-thiolase (3-KAT) is the last enzyme in theintramitochondrial pathway that is involved in the metabolismof fatty acids (fatty acid b-oxidation). There are 3 different 3-KAT enzymes, with different affinities for long, medium orshort chain fatty acids. Long-chain 3-KAT primarily acts onlonger chain fatty acid intermediates. Long-chain 3-KATinhibitors, such as trimetazidine, inhibit the activity of thisenzyme, thereby inhibiting fatty acid oxidation. Recentinterest has focused on 3-KAT inhibitors as a noveltherapeutic approach to protecting the ischemic heart.

Long-chain acyl-CoA synthetase

  • Long-chain acyl-CoA synthetase is one of the first enzymesin the fatty acid metabolic pathway. It converts long-chainfatty acids to long chain acyl-CoA within the cell. Longchainacyl-CoA is then either metabolized by themitochondria to produce energy, or is used to producemembrane and cellular lipids.

Luteinizing hormone

  • Luteinizing hormone (LH) is a heterodimeric glycoprotein consisting of α and β subunits, and has a molecular weight of 28-29 kDa. LH is synthesized and released by gonadotrophs in the anterior pituitary in response to stimulation by gonadotropin releasing hormone, itself released from hypothalamic neurons into the capillary networks of the hypothalamic median eminence and lower infundibular trunk. In males, LH stimulates Leydig cells in the testis to produce testosterone. In females, LH causes ovulation, the formation of the corpus luteum, and stimulation of the ovaries to produce estrogen and progesterone.

Lycopene

  • Lycopenes are antioxidants that are abundant in tomatoesand tomato juice. Clinical studies are presently assessingwhether lycopenes can be used to prevent free radicalinjury.

M1 macrophages

  • Macrophages are cells that arise from differentiated monocytes that have migrated into tissue. They are phagocytes that have a function in both innate and adaptive immunity. As macrophages are technically phagocytes, they play a primary role in phagocytosing cellular debris and pathogens. The M1 macrophage refers to the classically activated macrophages that act as immune effector cells and are traditionally proinflammatory (ie, they produce and release a number of proinflammatory cytokines), and are activated in response to endotoxins such as lipopolysaccharide.

M2 macrophages

  • The M2 macrophage in general is a term to describe a macrophage that is not the classically activated M1 macrophage (ie. alternatively activated macrophage), often referring to those macrophages that are involved in wound healing and tissue repair. M2 macrophages are able to tone down immune system responses by the production of anti-inflammatory cytokines such as IL-10 and IL-13.

Malonyl CoA decarboxylase (MCD)

  • MCD is an enzyme that controls malonyl CoA levels in anumber of different types of cells, particularly heart andskeletal muscle. MCD degrades malonyl CoA to acetylCoA. This is an important reaction, since malonyl CoA is apotent inhibitor of mitochondrial fatty acid uptake, andtherefore an important regulator of muscle fatty acidoxidation.

Malonyl-CoA

  • Malonyl CoA is a small molecule synthesized in cells byacetyl CoA carboxylase. Malonyl CoA has an important rolein regulating muscle fatty acid oxidation, secondary toinhibiting mitochondrial fatty acid uptake. It also is animportant substrate for fatty acid biosynthesis.

Malonyldialdehyde

  • p>Malonydialdehyde is a small molecule that is releasedfrom larger molecules, such as lipids, during oxidativestress. Measurement of the release of this compound isoften used as an index of the degree of free radicaloxidative stress to which a cell or organ is beingexposed.

Mammalian target of rapamyc in (mTOR)

  • mTOR is a protein kinase that senses the availability of amino acids and therefore responds to the nutritional status of the cell. mTOR regulates mRNA translation and protein synthesis, and is therefore of central importance in regulating cell division and proliferation. mTOR is the intracellular protein target of the fungal macrolide, rapamycin.

Mannose-6-phosphate

  • Mannose-6-phosphate is a sugar that is phosphorylated onits sixth carbon.

Matrix metalloproteinases (MMPs)

  • Matrix metalloproteinases (MMPs) are a family of extracellular matrix degrading enzymes that are involved in tissue remodeling. Alteration in MMP activity has been shown to contribute to ventricular remodeling in heart failure or following an acute myocardial infarction.

Membrane phospholipid turnover

  • Cellular membranes consist of a number of phospholipidsthat are arranged in a bilayer. There are a number ofdifferent phospholipids in these membranes. Thesephospholipids are not static and are constantly turningover. Some phospholipids, such as phosphatidyl inositol,can turnover quite rapidly, resulting in the production ofproducts that are important in cellular signalling processes(i.e. inositol triphosphate and diacylglycerol).

micro RNA (miRNA)

  • miRNAs are a class of highly conserved, endogenous, non-coding RNA molecules of approximately 22 nucleotides that silence gene expression at the post-transcriptional level by either promoting the degradation of messenger RNA (mRNA), or inhibiting the translation of protein from mRNA by translational repression.

Microcirculation

  • The microcirculation is comprised of several components of the vascular system, including arterioles, capillaries, and venules. The contractile state of arterioles is the major determinant of peripheral vascular resistance, whereas, the contractile state of ven ules influences venous return to the heart. The exchange of nutrients, gases, chemical mediators, and metabolic by-products between cells and the blood occurs via capillaries.

Microvascular dysfunction

  • Microvascular dysfunction (also known as small-vessel disease) occurs when damage arises in the walls and inner lining of the small coronary artery blood vessels that branch off from the larger coronary arteries (ie, left coronary artery). The damage in these smaller coronary artery blood vessels can produce spasms that decrease blood flow to the myocardium and thereby cause ischemia, and is more likely to develop in women.

Missense mutation

  • Mutations in the nucleotide sequence of DNA can result in thecoding of proteins with missense mutations in the amino acids.This can alter the primary amino acid sequence and proteinstructure of the protein. An example of missense mutations aremutations of the b-myosin heavy chain (MHC) gene that canlead in a number of mutations in the protein that can lead tohypertrophic cardiomyopathy.

Mitochondrial electron transport chain

  • The mitochondrial electron transport chain is a numberof mitochondrial proteins involved in energy production.Nicotinamide adenine dinucleotide (NADH) and reducedflavin adenine dinucleotide (FADH2) are used assubstrates for the electron transport chain. In the courseof oxidizing NADH and FADH2, protons are pumped outof the mitochondria. This sets up an electrochemicalgradient in which adenosine diphosphate isphosphorylated to adenosine triphosphate (ATP) (by anATP synthase) as protons flow back into themitochondria.

Mitochondrial K+-ATP channels

  • Mitochondrial ATP-sensitive potassium (KATP) channelsare potassium channels that are present in themitochondrial membrane of cells. These channels areinhibited by ATP. The opening of the mitochondrial ATPsensitiveK(+) (KATP) channels in the heart is believed tohave cardioprotective effects in the setting of ischemiaand ischemia and reperfusion. Despite a major researcheffort, the molecular characterization of the mitochondrialK+-ATP channel remains unknown.

Mitochondrial permeability transition pore(MPTP)

  • The MPTP is a protein pore that forms in the inner mitochondrial membrane during cellular stresses such as ischemia/reperfusion injury, resulting in mitochondrial swelling and subsequent cellular death via either apoptosis or necrosis.

Mitochondrial thioredoxin

  • Thioredoxin is an antioxidant enzyme that prevents theoxidation of thiol (sulfur) groups of proteins.

Mitogen activated protein kinases (MAPKs)

  • MAPKs are a highly conserved superfamily of proteins involved in signal transduction from the plasma membrane to intracellular targets. The three major MAPK subfamilies include the extracellular-regulated kinases (ERKs), p38 MAPKs, and the c-Jun N-terminal kinases (JNKs).

Mitogen-activated protein kinase (MAPK) cascade

  • The MAPK cascade involves a number of kinases that havediverse functions in cells. The inflammatory effects of tumornecrosis factor (TNF)-α in cells is mediated by signalingpathways involving MAPK’s. pathways. MAP-KAPK-1 (alsoknown as p90 ribosomal S6 kinase, p90rsk).The mitogen-activated protein kinase (MAPK)-activatedkinase, p90 ribosomal S6 kinase is a kinase in the MAPKcascade. p90 ribosomal S6 kinase is activated byphosphorylation, whereby it then participates in many cellularprocesses, including the regulation of protein synthesis.

Monobutyrin

  • Monobutryin is a novel angiogenic compound that issynthesized and secreted during the differentiation ofadipocytes. It has a major role as a differentiationdependentangiogenic molecule.

Monounsaturated fatty acids (MUFAs)

  • MUFAs are fatty acids that contain only one double bond in their carbon backbone. Oleic acid is one of the most important MUFAs because it circulates at the highest concentration in our body and is critical for energy metabolism.

mTOR pathway

  • Mammalian target of rapamycin (mTOR) is a kinase that is a member of the phosphatidylinositol kinase family. The mTOR pathway functions as a key signaling pathway involved in the control of cell growth and proliferation. mTOR is activated in response to a number of upstream signaling molecules, including insulin and growth factors such as IGF-1 and IGF-2. The term mTOR arose since rapamycin was originally shown to inhibit the mTOR pathway.

MVO2

  • Mixed venous oxygen saturation (MVO2) measures the end result of oxygen delivery and consumption at the tissue level. With regards to the heart MVO2 can be calculated according to the Fick principle, utilizing the arteriovenous oxygen difference and coronary flow rates, and reflects cardiac oxygen consumption where an increase in MVO2 indicates increased oxygen consumption.

Myocardial salvage

  • Amount of myocardium salvaged after an acute coronary artery occlusion by means of reperfusion or a therapeutic intervention applied at the onset of reperfusion in order to reduce myocardial infarct size.

Myocardin

  • Myocardin is a serum response factor transcriptional coactivator found specifically in cardiac and smooth muscle, which belongs to a family of transcription factors and plays a key role in inducing smooth muscle differentiation.

Myoglobin

  • Myoglobin is a single-chain globular protein of 153 or 154 amino acids related to hemoglobin that contains a heme (iron-containing porphyrin) prosthetic group in its center around which the remaining apoprotein folds. It binds iron and oxygen and is found in the muscle tissue of virtually all vertebrates and mammals.

Myosin

  • Myosin is one of the two main proteins involved in musclecontraction. It is a large protein that interacts with actin toform the muscle striations typical of muscle fibers. Slidingof myosin by actin is an important step in musclecontraction.

Myosin heavy chain

  • Myosin heavy chain is a key component of the contractileapparatus of muscle cells and comprises the thickfilament of muscle fibers. Sliding of myosin by actin(another major structure of contractile proteins) is animportant step in muscle contraction.

Na+/H+ exchanger

  • The Na+/H+ exchanger is a membrane ion transporter thatexchanges Na+ for H+. In the heart, it is one of a numberof pathways to extrude protons (H+) from the heart.However, this is coupled with a net inward flux of Na+.During and following ischemia, Na+/H+ exchanger activityincreases, due to the ischemic-induced increase inintracellular acidosis. The increased Na+/H+ exchangeractivity can lead to Na+ overload in the ischemic heart,which can decrease cardiac efficiency (energy is needed toextrude this Na+) and contribute to cell injury.

Na/K-ATPase and the SR-Ca++-ATPase

  • Na/K-ATPase and the SR-Ca++-ATPase are two ion pumpsthat are involved in the transport of ions acrossmembranes. They usually pump these ions against aconcentration gradient, and therefore energy is required,which is provided by the hydrolysis of ATP, the main energycurrency in cells (hence the name ATPases). Na/K-ATPasepumps Na+ out of cells, while simultaneously pumping K+into cells. The SR-Ca++-ATPase pumps Ca++ from thecytoplasm into sarcoplasmic reticulum vesicles. Inmuscle, this results in a lowering of cytoplasmic calciumand a relaxation of the muscle.

Nanoparticle tracking analysis

  • Nanoparticle tracking analysis allows for the visualization and analysis of particles in liquids by relating the rate of Brownian motion to particle size. This method is able to determine the size distribution of small particles in liquid suspension with a diameter of approximately 10 to 1000 nm.

Negative predictive value

  • Negative predictive value, with respect to diagnostic testing, is a conditional probability describing the proportion of patients with a negative test that are free of the target disease. Negative predictive value of a diagnostic test is calculated as a ratio: true negative value/(true negative value + false negative value).

Nicotinamide adenine dinucleotide (NAD+/NADH)

  • A coenzyme critical to life in all living cells that consists of two nucleotides joined through a phosphate group. One of the nucleotides possesses an adenine base, whereas the other possesses nicotinamide. As a coenzyme, it is involved in numerous redox reactions that occur in metabolism. One of its major roles is to act as a reducing agent and electron donor during the electron transport chain, which is critical to adenosine-5’-triphosphate (ATP) production during the process of oxidative phosphorylation.

Nicotinamide adenine dinucleotide (NADH) and the electron transport chain

  • Nicotinamide adenine dinucleotide (NADH) is animportant molecule that is both a substrate and a productof many biochemical reactions. In mitochondria, theproduction of NADH by the catabolism of fatty acids andcarbohydrates enters the electron transport chain. Theelectron transport chain transfers electrons through anumber of different enzyme complexes which catalyze thepumping of protons out of the mitochondrial matrix. Theseprotons can then pass back into the mitochondria via anenzyme called ATP synthase. The downhillelectrochemical gradient of this process produces energythat results in the production of ATP from ADP. ATP is aform of chemical energy used in most cellular processesrequiring energy.

Nicotinamide adenine dinucleotide (NADH)- coenzyme Q-oxidoreductase complex (complex I)

  • Nicotinamide adenine dinucleotide (NADH)-coenzyme Qoxidoreductasecomplex (complex I) is the first complex ofthe electron transport chain. It oxidizes NADH in the firstreaction of the electron transport chain.

NIH 3T3 fibroblasts

  • NIH 3T3 fibroblasts are a commonly used fibroblast cellline that was produced by the National Institutes ofHealth.

Nitric Oxide

  • Nitric oxide is a gaseous signaling molecule produced in the human body via the enzymatic activity of nitric oxide synthase. It has a number of important biological functions, one of its primary ones to act as a powerful vasodilator that induces smooth muscle cell relaxation. Pharmaceutical agents such as nitroglycerin, which are used for the treatment of angina, mediate their antiischemic effects by acting as precursors for nitric oxide biosynthesis.

Nitric oxide activates guanylyl cyclase

  • Guanylyl cyclase is the enzyme responsible for convertingguanylyl triphosphate to cyclic guanosine monophosphate(cGMP). One of the prominent effects of cGMP is smoothmuscle relaxation. Release of nitric oxide by endothelialcells is a potent vasodilator. The actions of nitric oxide arenow known to be due to a stimulation of guanylyl cyclase,that results in an increase in cGMP levels and smoothmuscle relaxation.

Nitric oxide synthase

  • Nitric oxide synthase is the enzyme responsible for theproduction of nitric oxide (NO). NO is a very importantmolecule in many cellular events and was identified as themolecule released by endothelial cells that can causevascular relaxation.

Nitric oxide–cyclic guanosine monophosphate (NOcGMP)axis

  • The nitric oxide–cyclic guanosine monophosphate (NO-cGMP) axis refers to the signaling transduction pathway mediated by the gaseous signaling molecule NO, which activates soluble guanylyl cyclase (sGC). NO induction of sGC activity leads to massive increases in the intracellular levels of the second messenger cGMP, which leads to activation of protein kinase G–mediated signaling events.

Nociceptor

  • A nociceptor is a receptor organ that is sensitive to stimulicapable of causing harm or injury. In response to thestimuli, the receptor would provide the sensation of pain(via neural transmission of the sensory stimulus from thereceptor to the brain).

Norepinephrine

  • Norepinephrine (sometimes called noradrenaline) is a catecholamine with multiple roles, including as a hormone and a neurotransmitter. Along with epinephrine (adrenaline), norepinephrine is also part of the fightor-flight response, and directly increases heart rate, triggers the release of glucose from energy stores, and increases blood flow to skeletal muscle. Norepinephrine also increases blood pressure by increasing vascular tone through α-adrenergic receptor activation. The actions of norepinephrine are carried out via binding to adrenergic receptors.

NT-proBNP

  • The N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is an inactive, 76-amino acid peptide derived for the cleavage of the 108-amino acid prohormone, proBNP, to the active hormone BNP, a 32-amino acid peptide. NT-proBNP is a sensitive biomarker of cardiac dysfunction, and can serve as a prognostic indicator in patients with stable coronary artery disease.

Nuclear transcription factor kappa-B (NFk-B)

  • NFk-B is a ubiquitous transcription factor that plays animportant integrating role in the intracellular regulation ofimmune response, inflammation and cell cycle regulation.NFk-B is activated by various stimuli, such as those thatare implicated in the progression of chronic heart failure.Signaling by NFk-B involves its release from inhibitorkappa B (IkappaB) in the cytosol, followed bytranslocation into the nucleus, where it affects genetranscription.

Nucleases

  • Nucleases are nuclear enzymes involved in thedegradation of nucleic acids chains.

Nucleoplasm

  • The nucleoplasm is the protoplasm of a cell containedwithin the nucleus. It is the compartment of the cell thatcontains the nuclear material, such as the chromosomes.

Ob/ob mouse

  • The leptin-deficient (ob/ob) mouse is a geneticallymutated mouse in which a leptin deficiency occurs. Thisleptin deficiency results in the development of a markedobesity, glucose intolerance and insulin-resistance. It is avery common experimental model in which to examine theconsequences of leptin deficiency on obesity and insulinresistance.

Orthophenylpentadecanoic acid (oPPA)

  • Orthophenylpentadecanoic acid (oPPA) is a fatty acidanalog that can be radiolabeled (eg. with 123I) and used asan imaging agent to assess fatty acid uptake into tissues.It is often used to determine whether fatty acid uptake isaltered in the hearts of patients. This is established byusing a gamma-camera to determine the amount ofradiolabeled oPPA taken up by the heart.

Osteopontin

  • Osteopontin is an abundantly expressed adipose tissue cytokine (adipokine) that plays a major role in inflammation, though it is also expressed in other cell types/tissues such as macrophages, smooth muscle cells, and skeletal muscle. Osteopontin regulates inflammation/immune function via modulating monocyte adhesion, migration, differentiation, and phagocytosis, whereas reducing osteopontin action has been shown to attenuate inflammation.

Osteoprotegerin

  • Osteoprotegerin is a cytokine receptor that is a member of the tumor necrosis factor receptor superfamily and acts as a receptor for the ligands receptor activator of nuclear factor κB ligand and tumor necrosis factor-related apoptosis-inducing ligand. Osteoprotegerin levels are elevated in patients with cardiovascular disease and thus osteoprotegerin may serve as a potential biomarker in the risk stratification of patients with cardiovascular disease.

Oxidative Stress

  • Oxidative stress in general is the deterioration in normal redox state primarily due to an imbalance between prooxidants and anti-oxidants sufficient to induce modification/damage of macromolecules. This results in the production of peroxides and free radicals that are often toxic to cells via damaging DNA, lipids, and proteins.

Oxygen

  • Oxygen is a chemical element characterized by the atomic number 8 (ie, its nucleus contains eight protons). With respect to aerobic energy substrate metabolism,diatomic oxygen (ie, O2) serves as the terminal electron acceptor in the mitochondrial electron transport chain, and is reduced to water in the process of oxidative phosphorylation, where the oxidation of reducing equivalents (NADH and FADH2) is coupled to the synthesis of ATP from ADP and inorganic phosphate.

Oxygen consumption

  • Oxygen consumption refers to the amount of oxygen that is utilized by the body per minute. Following inspiration, and alveolar exchange oxygen is transported by the cardiovascular system to systemic tissues and is utilized via oxidative phosphorylation to generate ATP. Oxygen consumption is typically reported in absolute units (ie, L/min) or it is normalized to body mass (mL/kg/min)

Oxygen radical scavenger enzymes

  • Oxygen-derived free radicals are highly reactivecompounds that can react with and damage cellularcomponents (lipid membranes, protein, and DNA/RNA). Inorder to protect the cell from these oxygen-derived freeradicals, cells have a number of different oxygen radicalscavenger enzymes that are used to neutralize these freeradicals.

Oxysterols

  • Oxyterols are oxygenated derivatives of cholesterol. Theyhave diverse biological activities, including binding toSREBP-1c and LXRs.

p38 and c-jun N-terminal and mitogen-activated protein kinases

  • Mitogen-activated protein kinases (MAPK) are importantcomponents of signaling modules activated byneurotransmitters, cytokines, and growth factors, as well aschemical and mechanical stressors. p38 MAPK is one of thesekinases that has diverse cellular function including mitogenicactivity, control of glucose metabolism, and activation ofapoptotic pathways. The c-Jun N-terminal kinase (JNK) branchof the MAPK signaling pathway also regulates cellulardifferentiation, stress responsiveness and apoptosis inmulticellular eukaryotic organisms.

Paraphenylpentadecanoic acid (pPPA)

  • Paraphenylpentadecanoic acid (pPPA) is a fatty acidanalog that can be radiolabeled (eg. with 123I) and used asan imaging agent to assess fatty acid uptake into tissues.It is often used to determine whether fatty acid uptake isaltered in the hearts of patients. This is established byusing a gamma-camera to determine the amount ofradiolabeled pPPA taken up by the heart.

PCI (percutaneous coronary intervention)

  • PCI is a non-surgical, revascularization procedure utilized in the setting of atherosclerotic coronary artery disease. PCI utilizes a catheter to place a stent into a stenotic coronary artery, to subsequently reduce coronary narrowing, and thus improve blood flow to regions of the myocardium distal to the atherosclerotic lesion.

Peak oxygen consumption (V.O2)

  • Peak oxygen consumption (VO2) refers to the highest value of oxygen consumption that is obtained in response to an increase in energy demand (ie, increased work/effort or exercise). Maximal oxygen consumption (VO2max) occurs when progressive increases in energy demand do not elicit further increases in oxygen consumption (ie, oxygen consumption has plateaued), and is a measure of mitochondrial function/aerobic capacity. VO2max is compromised in a number of clinical conditions including heart failure.

Perhexilene

  • Perhexilene is a compound that has found some use in thetreatment of angina pectoris (particularly in Australia). Itsexact mechanism of action is unknown, although it hasbeen suggested to inhibit fatty acid uptake into heartmitochondria by inhibiting an enzyme called carnitinepalmitoyltransferase-1.

Peroxides

  • Peroxides are chemical substances that contain a peroxounit - one that has an oxygen-oxygen bond (O–O) and thechemical formula of O22-. The most familiar example of aperoxide is hydrogen peroxide.

Peroxiredoxin III

  • Peroxiredoxin III is specifically localized to mitochondriaand is believed to play an important role in the regulationof cellular redox status by serving as a primary line ofdefense against H2O2 produced during respiration.

Peroxisome proliferator activated receptor alpha

  • Peroxisome proliferator activated receptor alpha (PPARα) is a nuclear receptor involved in the transcriptional regulation of proteins. PPARα has many functions, including regulating the expression of many enzymes involved in the control of fatty acid oxidation in muscle, heart and liver.

Peroxisome proliferator-activated receptor a (PPARα)

  • PPARα is a nuclear receptor involved in the transcriptionalregulation of proteins. PPARa has many functions,including regulating the expression of many enzymesinvolved in the control of fatty acid oxidation in muscle.

Peroxisome proliferator-activated receptor alpha (MHC-PPARα)

  • Peroxisome proliferator-activated receptor (PPARα) is anuclear receptor involved in transcriptional regulation ofproteins. PPA0052α has many functions, includingregulating enzymes involved in the control of fatty acidoxidation in the heart. MHC-PPARα refers to anexperimental approach that is used to selectively expressPeroxisome proliferator-activated receptor alpha inmuscle. This is achieved by linking the Peroxisomeproliferator-activated receptor a gene to the myosin heavychain (MHC) promoter. The production of transgenic micefrom embryonic stem cells that contain the MHC-PPARαgene will result in mice that overexpress PPARa targetedto muscle.

Peroxisome proliferator-activated receptorg (PPARγ)

  • Peroxisomal proliferators-activated receptors are nuclearreceptors involved in the transcriptional regulation ofproteins. One of these nuclear receptors is PPARγ, whichmodifies the expression of a number of proteins, includingthose involved in insulin sensitivity and lipid metabolism.Activation of PPARγ is a therapeutic approach to treatingdiabetes, which may in part be due lowering blood fattyacid levels, secondary to decreasing fatty acid release fromadipose tissue.

Peroxisome proliferator-activated receptors (PPARs)

  • PPARs are members of the ligand-activated nuclear receptor superfamily. In mammals, three distinct PPAR isoforms have been identified (PPARα, PPARγ, and PPARβ/d) with differential tissue distri- butions. PPARs regulate the expression of various enzymes involved lipid metabolism by forming heterodimers with retinoid X receptors and binding to PPAR response elements in the promoter region of target genes.

Peroxisome proliferator–activated receptor ƴ coactivator 1α (PGC1α)

  • PGC1α is a transcriptional coactivator that plays a key role in the regulation of cellular energy metabolism. Activation of PGC1α increases mitochondrial biogenesis. In muscle, PGC1α activation results in a muscle that is more oxidative and less glycolytic.

Peroxynitrite (ONOO-)

  • Peroxynitrite (ONOO) is formed by the combination of NOwith O2–. ONOO– then rapidly decomposes to form highlycreative oxidant species.

PGC-1α

  • Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a transcription co-activator that plays a key role in the regulation of cellular energy metabolism. Activation of PGC-1α increases mitochondrial biogenesis. In muscle PGC-1α activation results in a muscle that is more oxidative and less glycolytic.

Phosphatidylinositol (4,5) biphosphate (PtdIns(4,5)-P2)

  • Phosphoinositol-4,5-bisphosphate (PIP2) is an intracellularsignalling molecule produced by phosphoinositol-4-phosphate-5-kinase. PIP2 is produced by various stimuli, includingactivation of the insulin receptor. PIP2 then acts as a substratefor phosphoinositol 3-kinase (PI 3-K) to producePtdIns(3,4,5)-P3.

Phosphatidylinositol 3-kinase

  • Phosphatidylinositol 3-kinase is an intracellular kinaseactivated by lipids that phosphorylates the cellularphospholipid, phosphatidylinositol. The product of thisreaction is involved in many intracellular signalingpathways, including the control of energy metabolism.

Phosphocreatine

  • Phosphocreatine (PCr) is a high-energy phosphatecompound that functions to buffer intracellular ATP concentrations. When increases in energy demand deplete ATP, intracellular PCr is utilized to phosphorylate ADP, yielding ATP and creatine, a reversible reaction catalyzed by the enzyme cre- atine kinase (ie, ADP + H+ + PCr ↔ ATP + Cr). This reaction replenishes intracellular ATP at a rate that is greater than that of ATP generation from catabolic pathways.

Phosphodiesterase type 5 (PDE5)

  • Phosphodiesterases are enzymes that cleave cyclicnucleotides such as cAMP and cGMP. PDE5 is aphosphodiesterase isoform that cleaves cGMP. Inhibitionof PDE5 results in smooth muscle relaxation, and is thetarget for sildenafil (Viagra). This explains the coronaryvasodilatory effect of sildenafil, as well as the effects onpenial erection.

Phosphodiesterase type-5 (PDE5) inhibitors

  • PDE-5 is the enzyme that metabolises cyclic guanosinemonophosphate (cGMP). Therefore, PDE-5 inhibitors willprevent the degradation of cGMP and increase tissuelevels of cGMP. A well known example of a PDE-5 inhibitoris sildenafil (marketed as Viagra®). In addition to itssmooth muscle relaxing effects in the penis, sildenafil canalso induce pulmonary and coronary vasodilation,precondition the myocardium, reduce platelet activation,and potentially reduce early graft occlusion. As a result,PDE-5 inhibitors have potential in the treatment of bothpulmonary hypertension and ischemic heart disease.

Phosphofructokinase

  • Phosphofructokinase (PFK) is the rate-limiting enzymeinvolved in the glycolytic pathway. It is a highly regulatedenzyme that converts fructose 6-phosphate to fructose 1,6bisphosphate. Activation of PFK results in an activation ofglycolysis, while inhibition of PFK results in an inhibitionof glycolysis.

Phosphoinositide-dependent protein kinase-1 (PDK-1) and PKB (protein kinase B also known as Akt)

  • 3-phosphinositide-dependent kinase-1 (PDK-1) is asignaling kinase activated by PtdIns(3,4,5)-P3. Thiskinase then acts on downstream kinases such as PKB andprotein kinase C to mediate numerous cellular events.Protein kinase B is an intracellular kinase that is importantin regulating glucose metabolism. It is a kinasedownstream of PDK-1, and insulin activation of PKB willresult in GLUT-4 translocation to the cell membrane,thereby stimulating glucose uptake.

Phosphoribosylpyrophosphate

  • Phosphoribosylpyrophosphate is an intermediate in thepurine biosynthesis pathway. Purines are an importantcomponent of DNA and RNA.

Phosphorylation

  • Phosphorylation involves the addition of a phosphate (PO43-) to a protein/organic molecule via the action of enzymes known as kinases. Protein phosphorylation is one of the primary cellular mechanisms by which enzyme activity can be modified post-translationally.

Pituitary gland

  • The pituitary gland is a pea-sized endocrine gland consisting of three lobes (anterior, intermediate, and posterior) that protrudes from the bottom of the hypothalamus of the brain, and synthesizes and secretes a number of hormones that control/regulate growth (human growth hormone), blood pressure (vasopressin), sexual reproduction (FSH and LH), and pregnancy (oxytocin).

Plasminogen activator inhibitor (PAI)-1

  • Plasminogen activator inhibitor (PAI)-1 is a protein thatinhibits fibrinolysis and proteolysis. Increases in PAI-1levels have been associated with increased risk ofmyocardial infarction and decreased risk ofcerebrovascular events.

Pleckstrin homology domain

  • Pleckstrin homology (PH) domains are the 11th mostcommon domain in the human genome, and are bestknown as domains in an enzyme that have the ability totarget cellular membranes by binding specifically tophosphoinositides. Most PH domains are not capable ofindependent membrane targeting and usually require bothphosphoinositide and non-phosphoinositide determinantsfor their subcellular localization.

Pluripotency

  • Pluripotency refers to a stem cell with the ability to differentiate into any of the three germ layers (endoderm, mesoderm, and ectoderm). Furthermore, pluripotent stem cells can be further divided into completely pluripotent (ability to form every cell of the embryo proper) or partially pluripotent (ability to form cells of all three germ layers, but does not exhibit all the characteristics of a completely pluripotent stem cell).

Polyunsaturated fatty acids (PUFAs)

  • PUFAs are fatty acids that contain more than one double bond in their carbon backbone. The essential fatty acids, alpha-linolenic acid (omega-3 fatty acid) and linolenic acid (omega-6 fatty acid) represent two of the most important PUFAs as they cannot be synthesized endogenously in our bodies.

Positive predictive value

  • Positive predictive value, with respect to diagnostic testing, is a conditional probability describing the proportion of patients with a positive test that are positive for the target disease. Positive predictive value of a diagnostic test is calculated as a ratio: true positive value/(true positive value + false positive value).

Positron emission tomography-magnetic resonance imaging (PET-MRI)

  • Imaging that uses a combination of technologies to assess both morphology and function of the heart and vasculature. Magnetic resonance imaging is used to assess tissue morphology, while positron emission tomography is used to assess function.

PPARα

  • Peroxisome proliferator activated receptor α is a member of the ligand-activated nuclear hormone receptor superfamily. Fatty acids function as ligands for PPARα, and fatty acid-bound PPARα forms heterodimers with the retinoid X receptor. The PPAR-retinoid X receptor heterodimer can then translocate to the nucleus where it binds to PPAR response elements present in the promoter regions of target genes, including those involved in regulating fatty acid metabolism. PPARα is predominantly expressed in tissues that exhibit a high capacity to oxidize fatty acids including the liver, skeletal muscle, and heart.

Precision

  • Precision is a measure of the reproducibility of a measurement. Precision represents the closeness of agreement between independent measurements, and is commonly expressed as a coefficient of variation or standard deviation.

Primary percutaneous coronary intervention (PPCI)

  • A nonsurgical procedure aimed at restoring blood flow to an occluded or obstructed coronary vessel in acute coronary syndromes. This involves the insertion of a balloon or other device on a catheter through a femoral or radial artery to the occlusion site, where the artery is then opened to restore blood flow.

PRKAG2

  • PRKAG2 is the gene that encodes the g2 subunit of AMPactivatedprotein kinase (AMPK). Mutations in PRKAG2 haverecently been shown to cause cardiac hypertrophy, cardiacglycogen accumulation, Wolff-Parkinson-White syndrome,and conduction system disease causing pre-excitation.

Proanthocyanidins

  • Proanthocyanidins are components of grape seeds and arethe main phenolic antioxidant of red wine. They arethought to have beneficial antioxidant effects.

Proprotein convertase subtilisin/kexin type 9 (PCSK9)

  • PCSK9 is a protein that binds to the low-density lipoprotein (LDL) cholesterol receptor in the liver. PCSK9 binding to the LDL receptor results in breakdown of the LDL receptor, thereby increasing blood cholesterol levels. Thus, inhibition of PCSK9 to increase liver LDL-receptor expression and subsequent lowering of blood cholesterol levels has been pursued for the treatment of high cholesterol. Some approved agents include alirocumab and evolocumab.

Prostacyclin

  • Prostacyclin is a prostaglandin that has a number ofimportant biological effects, one of which is a potentvasodilatory action in blood vessels.

Prostaglandins, thromboxanes and leukotrienes

  • Prostaglandins, thromboxanes and leukotrienes arederivatives of arachidonic acid, and belong to a class ofbiologically active lipids called eicosanoids. They havediverse effects in the body, including vasodilation,vasconstriction, clot formation and mediators ofinflammation.

Prostate-specific antigen

  • Prostate-specific antigen (PSA) is a member of the kallikrein (KLK)-related peptidase family, and is also known as KLK3. PSA is a serine protease synthesized in prostate cells as 261 amino acid preproprotein, which is subsequently processed to a 244 amino acid pro-PSA. Pro-PSA is processed via cleavage of a seven amino acid peptide to yield mature/active PSA, which circulates as an 80-90 kDa complex with α-1-antichymotrypsin. PSA is widely used as a tumour marker, as cancerous prostate tissue releases up to 10-fold greater amounts when compared with normal and benign hyperplastic prostate tissue, despite similar levels of overall expression.

Protein carbonyls

  • Free radicals can target lipids, DNA or proteins. One of theproducts of free radical damage to proteins is theformation of protein carbonyls. Oxidatively modified formsof proteins accumulate during oxidativestress.

Protein kinase (AMPK) pathway

  • AMP-activated protein kinase (AMPK) is a widelydistributed cellular kinase that is activated during times ofmetabolic stress. It has been termed a cellular “fuelgauge”, and primarily functions to turn off energyconsumingpathways and turn on energy-producingpathways during metabolic stress.

Protein kinase B (PKB)

  • Protein kinase B (PKB) is an intracellular kinase that isimportant in regulating glucose metabolism. It is a kinasedownstream of PI3K, and insulin activation of PKB willresult in GLUT4 translocation to the cell membrane,thereby stimulating glucose uptake.

Protein kinase C (PKC)

  • Protein kinase C (PKC) is an important kinase involved incellular signaling. It is activated by lipids (diacylglycerols)released from the phospholipids membrane. There is aconsiderable research interest in the role of PKCmodification in the ischemic heart.

Proteins of the Rho-family

  • The Rho-family of proteins are proteins involved in cellularsignalling. An example of this is Rho A, which is involvedin vascular smooth muscle proliferation. Platelet-derivedgrowth factor can increase Rho A protein. Rho kinase playsan important role in this process as an effector of Rho A.The RhoA/Rho kinase pathway can mediate calciumsensitization in vascular smooth muscle.

Proteinuria

  • Proteinuria refers to the excess presence of serum proteins (eg, albumin) in the urine, and typically occurs following glomerular lesions.

Proteosomes

  • Proteosomes are large protein complexes inside cells that function to degrade damaged proteins. Proteases in the proteasome degrade these proteins into short amino acid peptides.

Proto-oncogene Cbl

  • Cb1 is a protooncogene product that was initiallyidentified as part of a murine retrovirus transformingprotein. Cb1 is ubiquitously expressed protein containinga set of sequences providing interactions with a wide rangeof receptor and nonreceptor tyrosine kinases and signalingproteins. These properties permit Cb1 to take part in manyprotein-protein interactions as an adaptor, which formsmultimolecular signaling complexes, and coordinates theactivity of its components.

Protocatechuic acid

  • Protocatechuic acid is a naturally occurring antioxidant. Itis a phenolic compound found in various plants, includinggrapes.

PtdIns(3,4,5)-P3

  • PtdIns(3,4,5)-P3 is released from membranephosphatidylinositol as part of a signaling cascadeinitiated by a number of different hormones, includinginsulin. PtdIns(3,4,5)-P3 activates downstream targets,such as 3-phosphinositide-dependent kinase-1 (PDK-1).This kinase then acts on downstream kinases such as PKBand protein kinase C to mediate numerous cellular events.

Pyruvate

  • Pyruvate is an intermediate molecule in the metabolism ofboth glucose and lactates. Glycolysis produces twopyruvate molecules from each molecule of glucosemetabolized. Lactate can also be converted to pyruvate bythe enzyme lactate dehydrogenase. In the heart, much ofthe pyruvate produced is taken up by the mitochondriaand used by pyruvate dehydrogenase to produce acetylcoenzyme A.

Pyruvate dehydrogenase (PDH)

  • Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme that catalyzes the committed step of pyruvate oxidation (i.e., oxidative decarboxylation), thereby generating acetyl coenzyme A (CoA) for the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH) for the electron transport chain. PDH is part of a multienzyme complex, consisting of PDH kinase and PDH phosphatase. Phosphorylation of PDH by PDH kinase inhibits its activity, while dephosphorylation by PDH phosphates increases its activity. PDH activity is also sensitive to inhibition by substrate/product ratios as decreased ratios of NAD+/NADH and CoA/ acetyl- CoA decrease the rate of pyruvate oxidation.

Pyruvate dehydrogenase (PDH) kinase

  • Pyruvate dehydrogenase (PDH) kinase is anintramitochondrial kinase that phosphorylates and inhibitsPDH. Since PDH is the ratelimiting enzyme for themitochondrial metabolism of carbohydrates, activation ofPDH kinase will result in a decrease in the mitochondrialmetabolism of carbohydrates. Maintaining mitochondrialglucose metabolism is an important therapeutic strategy toprotect the ischemic heart. Therefore, inhibition of PDHkinase is a potential therapeutic approach to treatingischemic heart disease.

Pyruvate dehydrogenase complex (PDH)

  • The PDH complex is composed of a number of enzymeswhose function is to convert pyruvate (which mainlyoriginates from glycolysis or lactate dehydrogenase) andCoA into acetyl CoA. In the process, NAD+ is reduced toNADH. The acetyl CoA produced enters the tricarboxylicacid cycle where it is further metabolized, whereas NADHis used as an electron donor by the mitochondrial electrontransport chain. PDH is the rate-limiting step in glucoseoxidation.

Pyruvate dehydrogenase kinase 2

  • Pyruvate dehydrogenase kinase 2 (PDK2) is an intramitochondrial kinase that phosphorylates and inhibits pyruvate dehydrogenase (PDH). As PDH is the rate-limiting enzyme for the mitochondrial metabolism of carbohydrates, activation of PDK2 will result in a decrease in the mitochondrial metabolism of carbohydrates. Maintaining mitochondrial glucose metabolism is an important therapeutic strategy to protect the ischemic heart. Therefore, inhibition of PDK2 (which is expressed in the heart) is a potential therapeutic approach to treating ischemic heart disease.

Randle Cycle

  • The Randle Cycle is a metabolic phenomenon characterized via substrate competition between carbohydrate (glucose) and fatty acids for entry into oxidative pathways (the Krebs Cycle) for subsequent energy metabolism. As the oxidation of one substrate increases, it results in decreased oxidation of the competing substrate.

Receiver operator characteristic

  • Receiver operator characteristic (ROC) is a graphical plot that highlights a binary classifier system’s performance amidst varying discrimination thresholds. Plotting the true positive rate against the false positive rate at several threshold settings will result in the generation of an ROC plot.

Reduced nicotinamide adenine dinucleotide phosphate oxidase

  • Reduced nicotinamide adenine dinucleotide phosphateoxidase is an enzyme present in phagocytes such asneutrophils and macrophages. This enzyme is animportant source of free radicals.

Remote ischemic conditioning

  • An endogenous cardioprotective phenomenon in which brief cycles of nonlethal ischemia and reperfusion applied to an organ or tissue remote from the heart render the myocardium tolerant of a subsequent, otherwise lethal, episode of acute ischemia/reperfusion injury.

Renin

  • Renin is an enzyme that participates in the body’s reninangiotensin system (RAS) and mediates blood volume and arterial vasoconstriction. It is therefore an important regulator of blood pressure. Renin is secreted by the kidney granular cells of the juxtaglomerular apparatus and hydrolyzes angiotensinogen secreted fromthe liver into the peptide angiotensin I. Angiotension I is then converted by endothelial-bound angiotensin converting enzyme (ACE) into angiotensin II, a potent constrictor of blood vessels.

Renin angiotensin system (RAS)

  • RAS is the physiological hormone system responsible for the regulation of blood pressure and fluid balance. Renin (originating from the kidneys) stimulates the production of angiotensin, which induces blood vessel constriction and increases blood pressure. Angiotensin also stimulates the production of aldosterone, which acts on the kidneys to increase sodium and water reabsorption into the blood, also contributing to an increase in blood pressure.

Reperfusion injury

  • Reperfusion injury is a term used to describe injury that canoccur to the heart muscle during the period of reperfusionfollowing ischemia. As an example, an excessive reliance of theheart on fatty acids during reperfusion or the generation ofoxygenderived free radicals can cause muscle injury duringreperfusion of the ischemic heart.

Reperfusion injury salvage kinase (RISK) pathway

  • The RISK pathway is acytoprotective kinase signaling pathway comprised of the pro-survival kinases phosphotidly-inositol 3-kinase, Akt, and the extracellular regulated mitogen activated protein kinases (ERK1/2). It is implicated in limiting myocardial ischemia reperfusion injury.

Resistance

  • In the vascular system, resistance describes the mechanical factors that must be surmounted to propel blood through the circulatory system. Resistance is primarily determined by the contractile state/diameter of the arterioles.

Resistin

  • Resistin is an adipose tissue-specific factor which is reportedto induce insulin resistance, linking diabetes to obesity.

Reverse transcriptase

  • A reverse transcriptase is a type of enzyme responsible for the synthesis of DNA that is complementary to a single-stranded RNA template. The process of reverse transcription is critical to the life-cycle of retroviruses.

Rheumatoid factor

  • Rheumatoid factor is an autoantibody (antibody that targets the host organism’s own tissues) against the Fc portion of immunoglobulin, and this rheumatoid factor/ immunoglobulin immune complex is the most relevant autoantibody complex in the development of rheumatoid arthritis.

RNA-induced silencing complex

  • The RNA-induced silencing complex (RISC) is a multiprotein complex that incorporates one strand of small interfering RNA or microRNA and uses it as a template to recognize complementary messenger RNA. Upon recognition of the complementary strand, the RISC subsequently activates a protein within its multiprotein complex known as argonaute, which cleaves the RNA.

Ryanodine

  • Ryanodine is an inhibitor of the calcium channel that releasescalcium from the sarcoplasmic reticulum. It was an importanttool in first characterizing this channel, which is often calledthe ryanodine-sensitive calcium channel.

Sarcoplasmic reticulum

  • The sarcoplasmic reticulum is an intracellular organelle inheart and skeletal muscle that stores calcium. Duringexcitation-contraction coupling, release of calcium fromthe sarcoplasmic reticulum is the major source of calciumthat initiates muscle contraction.

Saxagliptin

  • Saxagliptin is an orally taken dipeptidyl peptidase-4 (DPP-4) inhibitor codeveloped by Bristol-Myers Squibb and AstraZeneca for the treatment of type 2 diabetes under the trade name Onglyza. Of interest, saxagliptin was shown to increase hospitalization rates for heart failure during the “Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis In Myocardial Infarction 53 (SAVOR-TIMI 53)” clinical trial.

Saxagliptin

  • Saxagliptin is an orally taken dipeptidyl peptidase-4 (DPP-4) inhibitor codeveloped by Bristol-Myers Squibb and AstraZeneca for the treatment of type 2 diabetes under the trade name Onglyza. Of interest, saxagliptin was shown to increase hospitalization rates for heart failure during the “Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis In Myocardial Infarction 53 (SAVOR-TIMI 53)” clinical trial.

secretory phospholipase A2 (sPLA2)

  • The phospholipase A2 family of enzymes specifically release fatty acids from the second carbon group of glycerol by hydrolysis of the sn-2 ester bond of phospholipids in cell membranes and circulating lipoproteins, resulting in the generation of arachidonic acid and lysophospholipids. sPLA2 is the secreted, extracellular form of the enzyme, and has been shown to promote inflammation in the vasculature and to correlate positively with the incidence of coronary artery disease. sPLA2 inhibition has thus been pursued as a target for the reduction of cardiovascular risk.

Sensitivity

  • Sensitivity is also known as “true positive rate,” and is a statistical measure of the performance of a binary classification test, which measures the percentage of actual positive outcomes/end points that are correctly identified as being a positive outcome/end point, hence the “true positive rate.”

SERCA

  • SERCA stands for sarcoplasmic/endoplasmic reticulumcalcium ATPase. SERCA is the enzyme primarily involvedin the transport of calcium into intracellular sarcoplasmicreticulum and endoplasmic reticulum. The sarcoplasmicreticulum (SR) is an intracellular organelle in heart andskeletal muscle that stores calcium. During excitationcontractioncoupling, release of calcium from the SR is themajor source of calcium that initiates muscle contraction.

SERCA2

  • Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) is the enzyme primarily responsible for the transport of calcium into intracellular sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER). SR is an intracellular organelle in heart and skeletal muscle that stores calcium. During excitation-contraction coupling, release of calcium for the SR is the major source of calcium that initiates contraction. SERCA2 initiates relaxation of muscle by re-sequestering the calcium back up into the SR.

Serine/threonine kinase

  • Kinases are proteins that phosphorylate other proteins,usually resulting in a modification of that protein'sfunction. Serine/threonine kinases are protein kinases thatphosphorylate proteins on serine or threonine amino acids.

Serotonin receptor (5-HT(1D)-)

  • Serotonin (5-hydroxytryptamine or 5-HT) is a transmitterin the central nervous system, and also functions in theperiphery as a ubiquitous hormone involved invasocontriction and platelet function. Serotonin acts on avariety of serotonin receptors, one of these being the 5-HT1D receptors.

Sevoflurane [1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane]

  • Sevoflurane is a volatile liquid that is utilized as an inhalation anesthetic to induce and maintain general anesthesia.

Signalling pathways

  • In all cells, complex signalling pathways exist whichmediate cell function. Many of these signalling pathwaysinvolve kinases that mediate numerous cellular actions,including the effects of hormones binding to receptorswhich translate into cellular actions. p38 and c-junN-terminal mitogen-activated protein kinases andcalmodulin dependent kinase (CamKII) are examples ofkinases involved in important signalling pathways.

Silent ischemia

  • Myocardial ischemia describes the situation where the heart/myocardium does not receive enough blood through the coronary circulation. The reduced blood flow and subsequent lack of oxygen delivery to the myocardium produces the sensation of chest pain, which is known as angina. If an individual does not experience the sensation of pain, it is referred to as “silent ischemia.” Individuals who have experienced previous heart attacks or are diabetic are at increased risk for developing silent ischemia.

Sirtuin proteins (SIRTs)

  • SIRT proteins are orthologues of the silent information regulator 2 (Sir2) gene family, which is conserved from bacteria to humans. SIRTs are either class III histone deacetylases/NAD+-dependent lysine deacetylases (SIRT1, -2, -3, -5, -7) or ADP-ribosyltransferases (SIRT4, -6) with varying subcellular localization. SIRTs have been implicated in regulating lifespan/longevity in lower organisms. They are also important regulators of a variety of processes in mammalian cells including signal transduction, cellular transport, gene transcription, and metabolism.

Sitagliptin

  • Sitagliptin is an orally taken dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Merck & Co. for the treatment of type 2 diabetes under the trade name Januvia. On October 2006, sitagliptin became the first DPP-4 inhibitor approved in the United States by the US Food and Drug Administration for the treatment of type 2 diabetes.

Sitagliptin

  • Sitagliptin is an orally taken dipeptidyl peptidase-4 (DPP-4) inhibitor developed by Merck & Co. for the treatment of type 2 diabetes under the trade name Januvia. On October 2006, sitagliptin became the first DPP-4 inhibitor approved in the United States by the US Food and Drug Administration for the treatment of type 2 diabetes.

Smooth muscle actin (alpha-)

  • α-Smooth muscle actin is a contractile protein involved inthe contraction of smooth muscle cells.

Sodium excretion

  • Sodium is filtered by the kidney and can be excreted in the urine. Sodium excretion is measured in terms of plasma and urine sodium, rather than by the interpretation of urinary sodium concentration alone, as urinary sodium concentrations can vary with water resorption. Therefore the urinary excretion rate can be used to get a measure of renal clearance. Sodium excretion is used in acute renal failure in order to determine if hypovolemia or decreased effective circulating plasma volume is a contributor to renal failure.

Specificity

  • Specificity is also known as “true negative rate,” and is a statistical measure of the performance of a binary classification test, which measures the percentage of actual negative outcomes/end points that are correctly identified as being a negative outcome/end point, hence the “true negative rate.”

SREBP-1c

  • Sterol regulatory element-binding protein (SREBP)-1c is akey regulator of fatty acid metabolism and plays a pivotalrole in the transcriptional regulation of different lipogenicgenes mediating lipid synthesis. Emerging evidencesuggests that insulin resistance and its associatedmetabolic dyslipidemia result from perturbations in theexpression of SREBP-1c, inducing lipogensis andproduction of VLDL particles.

ST-segment elevation myocardial infarction (STEMI)

  • Acute myocardial infarction caused by complete acute coronary artery occlusion, most often due to a thrombotic occlusion forming at the site of a ruptured atherosclerotic plaque in one of the major coronary arteries.

Stearoyl-CoA desaturase-1 (SCD1)

  • Stearoyl-CoA desaturase (SCD)1 catalyzes the ratelimitingreaction of monounsaturated fatty acid synthesis and plays animportant role in the development of obesity. SCD1 issuppressed by leptin but induced by insulin. SCD-1 expressionis also under the control of SREBP-1c. Studies have shownthat inhibition of SCD1 can prevent the development of highfatdietinduced obesity and hepatic steatosis.

Steatosis

  • Steatosis is the accumulation of lipids (usually neutral lipids, such as triacylglycerol [TAG] and cholesterol) in a cell in higher than normal amounts. For example, increased TAG levels in the heart is referred to as cardiac steatosis and in the liver is referred to as hepatic steatosis.

Strain measured by MRI

  • Magnetic resonance imaging is a sophisticated techniquethat produces high-quality images of the body. Newer MRItechniques allow for high resolution of the heart structureand chamber dimensions. Strain measured by MRI is anapproach to investigate heart function and wall tension.

Substance P

  • Substance P is a tachykinin and physiologically acts as aneurotransmitter and neuromodulator in the nervoussystem. Pathologically, it can also trigger malignant cellsto release cytokines and increase cell proliferation rates.

Subtypes (A1 and A2) of surface membrane P1 receptors

  • Purinergic receptors (designated “P” receptors) use purinenucleotides as ligands. The P1 class of purinergicreceptors use adenosine as a ligand. These P1 receptorscan further be classified as A1, A2, and A3 receptors. Thevasodilatory effects of adenosine are primarily mediated bybinding to A2 receptors. The direct chronotropic effects ofadenosine on the heart, and many of its cardioprotectiveactions are mediated by adenosine binding to A1receptors. Ischemic preconditioning involves a series ofintracellular events that are initiated with the activation ofthe A1 receptor, and end at the sensitive K+ ATP channelsof the mitochondria. New evidence points to a role foradenosine in promoting neovascularization through amechanism that requires interaction between theadenosine receptor subtype 2A (A(2A)R).

Superoxide

  • Superoxide is a free radical. It is an oxygen molecule thathas an unpaired electron. This molecule can react withlipids, proteins, DNA, and RNA, causing tissue damage.

Survivor activating enhancer (SAFE) pathway

  • The SAFE pathway is a cytoprotective kinase signaling pathway that requires the activation of signal transducer and activator of transcription 3 (STAT-3) and is implicated in limiting myocardial ischemia reperfusion injury.

T1 mapping

  • T1 mapping is a new noninvasive cardiac magnetic resonance imaging technique that can be performed with or without contrast and is useful in characterizing myocardial tissue properties such as increased extracellular volume in conditions such as hypertrophic cardiomyopathy and aortic stenosis. It can also noninvasively detect myocardial fibrosis.

TC10 family of Rho GTP-binding proteins

  • The Rho GTPases are related to the Ras proto-oncogenes andconsist of 22 family members. These proteins have importantroles in regulating the organization of the actin filamentsystem, and thereby the morphogenesis of vertebrate cells aswell as their ability to migrate. Signal initiation from theinsulin receptor and a series of adapter proteins result in theactivation of the G protein TC10. TC10 can influence anumber of cellular processes, including changes in the actincytoskeleton, recruitment of adapter proteins CIP4, andassembly of the exocyst complex. These events play crucialroles in the trafficking, docking and fusion of vesiclescontaining the insulin-responsive glucose transporter Glut4 atthe plasma membrane.

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)

  • Terminal deoxynucleotidyl transferase-mediated dUTPnick-end labeling (TUNEL) is an assay used to detectdouble-strand DNA breaks. This assay is used for in situidentification of apoptotic cells by detecting DNA damage.

Testosterone

  • Testosterone is an anabolic steroid hormone (derived from cholesterol). In males, testosterone is required for the development of secondary sexual characteristics and spermatogenesis. In the bloodstream, the majority of testosterone is tightly bound to sex hormone-binding globulin (SHBG), weakly bound to albumin (and other proteins), or freely circulating. Only a minor fraction of testosterone in the circulation is free/nonprotein bound. Testosterone that is not bound to SHBG (ie, albumin bound and free testosterone) is considered to be bioavailable. Several algorithms have been developed to calculate free testosterone concentration. If the circulating concentration of SHBG (nmol/L) and total testosterone (nmol/L) is measured, an estimate of circulating free testosterone concentration (nmol/L) can be calculated as follows: [Free testosterone] = [Total Testosterone] (6.11 – 2.38 log10 [SHBG])

Thermogenesis

  • Thermogenesis is the process by which an organism produces heat. This occurs either via shivering thermogenesis, where heat is produced from the conversion of the chemical energy of adenosine triphosphate (ATP) into kinetic energy, and some of this produced energy is lost as heat, or via nonshivering thermogenesis, which occurs primarily in brown adipose tissue and involves the actions of uncoupling protein 1 (UCP1). UCP1 is present in the inner mitochondrial membrane of cells and dissipates the proton gradient across this membrane. As a result of this action, mitochondrial respiration produces heat instead of ATP.

Thiazolidinediones (TZDs)

  • TZDs are a class of drugs that act as ligands for PPARγ. Anexample of a TZD is rosiglitazone. Activation of PPARγ byTZDs can improve muscle insulin sensitivity. They also canhave beneficial effects on blood lipids and vascularsmooth muscle lipid accumulation.

Thiobarbituric acid-reacting substances (TBARS)

  • Thiobarbituric acid-reacting substances (TBARS) is asimple assay that is used to measure malonyldialdehyde,a product of free radical lipid peroxidation.

Thioheptadecanoic acid

  • Thioheptadecanoic is a 16-carbon fatty acid that can beradiolabeled and used as a tracer for fatty acid uptake intothe heart. One of the radiolabels that can attached toheptadecanoic acid is an 18fluoro group resulting in18-fluoro-thioheptadecanoic acid (FTHA). A gammacameracan then be used to measure FTHA uptake into theheart. This approach is used to assess fatty acidmetabolism in the heart.

Thioredoxin peroxidase

  • Thioredoxin peroxidase is a peroxiredoxin that uses thiolsas reductants. Since they use hydrogen peroxide as asubstrate, they are an antioxidant enzyme.

Thioredoxin reductase

  • Thioredoxin reductase is a major cellular protein disulfidereductase. This enzyme has antioxidant activity.

Thrombomodulin

  • Thrombomodulin is a key component of the anticoagulantprotein C pathway and is a major contributor to vascularthromboresistance. It inhibits blood coagulation.

Thromboxane A2

  • Thromboxane A2 is a product of the cyclooxygenase pathway of arachidonic acid metabolism. In that pathway, cyclooxygenase catalyzes the production of prostaglandin H2 (PGH2) from arachidonic acids; PGH2 can then be used in the formation of a number of different eicosanoid products, including prostaglandins. Metabolism of PGH2 by thromboxane synthase, which is abundant in lung and platelets, results in the production of thromboxane A2. Thromboxane A2 has a variety of biological effects, including vasoconstriction and promotion of platelet aggregation.

Thromboxane A2

  • Thromboxane A2 is a product of the cycloxygenasepathway of arachidonic acid metabolism. The productionof PGH2 from arachidonic acids by cycloxygenase can beused for a number of different eicosanoid products,including the production of prostaglandins. Metabolism ofPGH2 by thromboxane synthase, which is abundant inlung and platelets, results in the production ofthromboxane A2. Thromboxane A2 has a variety ofbiological effects, including vasoconstriction andpromotion of platelet aggregation.

Tissue factor pathway inhibitor

  • Tissue factor pathway inhibitor is a critical inhibitor thatmodulates tissue factor-induced coagulation.

Tissue plasminogen activator

  • Tissue plasminogen activator is a thrombolytic agent thatdisrupts blood clots. It is widely used to break upthrombus in patients with acute myocardial infarction orstrokes.

TNF-α

  • Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine produced primarily by macrophages (also by other cells of the immune system, cardiac myocytes, adipocytes, fibroblasts, neurons). TNF-α is produced as a 216-amino-acid transmembrane protein arranged as homotrimers. The metalloproteinase, TNF-α converting enzyme (TACE/ADAM17) proteolytically cleaves transmembrane homotrimers, releasing soluble, 51-kDa TNF-α homotrimers. Both transmembrane and soluble TNF-α are biologically active, exerting effects via the activation of two receptor subtypes, TNFR1 (transmembrane, soluble TNF-α homotrimers) and TNFR2 (transmembrane TNF-α homotrimers).

Tocopheroxyl radical

  • Tocopheroxyl radicals are formed from a-tocopherol(vitamin E). Vitamin E is an antioxidant, since it is anefficient scavenger of lipid peroxyl radicals. Tocopheroxylradicals are formed during this process, which can then berecycled back to a-tocopherol.

Transfection

  • In molecular biology, the term transfection usually refersto the introduction of foreign DNA or RNA into a cell,resulting in the expression of a protein encoded by thatDNA or RNA.

Transforming growth factor (TGF)-β

  • Transforming growth factor (TGF)-β is a growth factor thathas an important role in controlling fibroblast growth andaccumulation of extracellular matrix proteins. Increases inTGF-β have been implicated in the maladaptive responseto cardiac hypertrophy.

Transforming growth factor β (TGF-β)

  • Transforming growth factor (TGF)-β is a growth factor that has an important role in controlling fibroblast growth and accumulation of extracellular matrix proteins. Increases in TGF-β have been implicated in the maladaptive response to cardiac hypertrophy.

Transporters

  • These are integral membrane proteins involved in mediating the movement of molecules across the cell membrane. Facilitative transporters move molecules down a concentration gradient, while active transporters couple the hydrolysis of ATP to the movement of molecules against their concentration gradient.

Trastuzumab

  • Trastuzumab is a monoclonal antibody that inhibits HER2/neu receptor signaling. As HER2/neu receptors are often overexpressed in certain cancers (such as breast cancer), trastuzumab has been explored as a therapeutic option in this pathology. Therapeutic utility of this agent may be limited due to its potential to induce cardiac dysfunction.

Triacylglycerol

  • Triacylglycerol (TAG) is the major storage form of fatty acids in the body and consists of three fatty acids attached to a glycerol backbone. Fatty acid storage in adipocytes primarily occurs in the form of TAG. The heart also contains sizable TAG stores as a source of fatty acids for energy production.

Triacylglycerol

  • Triacylglycerol is the major storage form of fatty acids inthe body and consists of three fatty acids attached to aglycerol backbone. Fatty acid storage in adipocytesprimarily occurs in the form of triacylglycerol. The heartalso contains sizable triacylglycerol stores as a source offatty acids for energy production.

Trimethylamine-N-oxide (TMAO)

  • TMAO is an organic amine oxide, which is formed from the oxidation of trimethylamine and hydrogen peroxide via the catalytic activity of flavin monooxygenase. TMAO may act as an important osmoregulatory compound affecting buoyancy and potentially protecting protein function under high pressure in fish. Recent studies in animals and humans also suggest that TMAO may act as a proatherogenic compound, and elevated TMAO levels are positively associated with increased cardiovascular risk in both rodents and humans.

Troglitazone

  • Troglitazone is an agonist of PPARγ. It belongs to a classof compounds called thiazolidinediones. Activation ofPPARγ ?with troglitazone has potential clinical applicationin the treatment of insulin resistance and atherosclerosis

Troponin(s)

  • Troponin(s) are a complex of three regulatory proteins (troponin C/I/T) essential for muscle contraction in skeletal and cardiac muscle. Troponin(s) (troponin-1 and troponin-2) are heterotrimeric complexes present in striated muscle (skeletal and cardiac muscle) that is comprised of a Ca2+ binding sub-unit (troponin-C), an inhibitory sub-unit (troponin-1), and an elongated troponin molecule (troponin-2) which binds both troponin-C and troponin-1. In conjunction with tropomyosin, the troponin eterotrimer forms a regulatory complex that controls the interaction of actin and myosin. The binding of Ca2+ to troponin permits muscle contraction. Cardiac troponins (troponins 1 and 2) are released from cardiac myocytes following myocardial damage and loss of membrane integrity, and serve as highly sensitive and specific biomarkers for establishing the diagnosis of myocardial infarction.

Tryptophan-rich sensory protein (TspO)

  • Tryptophan-rich sensory protein (TspO) is a tryptophan-richprotein that negatively affects the transcriptionalexpression of several genes.

Tubulin

  • Tubulin is a protein that forms a hollow cylindricalstructure that is important for the cytoskeleton of cells. a-And b-tubulin subunits form a helical array that makes upthe cytoskeletal structure.

Tumor necrosis factor (TNF-α)

  • Tumor necrosis factor (TNF-α) is a cytokine that acts viareceptors to mediate a number of biological effects,including the inflammatory response. The role of cytokinesin the pathogenesis of systolic heart failure (HF) has beenwell established. TNF-α can also activate the intrinsicmitochondrial death pathway that is responsible for thecardiac myocyte apoptosis.

Tyrosine kinases

  • Tyrosine kinases are enzymes that catalyze the transfer of the y-phosphate from adenosine triphosphate (ATP) to the hydroxyl oxygen of the tyrosine side chains on proteins. By doing so tyrosine kinases can phosphorylate tyrosine residues present with in specific motifs of various protein substrates.

Ubiquinol-10

  • Ubiquinol-10 is a reduced form of coenzyme Q.

Ubiquinol-cytochrome c reductase (complex III)

  • Ubiquinol-cytochrome c reductase is the third complex ofthe electron transport chain. It is involved in mitochondrialrespiration, which is a major source of energy for cells.

Ubiquinone

  • Ubiquinone (often called coenzyme Q10) is a quininecompound that serves as an electron carrier betweenflavoproteins. Ubiquinone is a component of the oxidativephosphorylation process in mitochondria that converts theenergy from fatty acids and carbohydrates into ATP (themain source of energy used to drive cellular machinery andsynthesis). An additional role of ubiquinone is that it actsin its reduced form (ubiquinol) as an antioxidant.

Ubiquitin ligases

  • Ubiquitin ligases are enzymes in cells that catalyze the ubiquitination reaction. These ubiquitinated proteins are then targeted for degradation by proteasomes. As a result, ubiquitine ligases are key enzymes involved in cellular protein degradation.

Ubiquitination

  • Ubiquitination is a process in cells in which proteins are “tagged” with a small protein called ubiquitin. This can lead to further ubiquitination of the protein, which then targets the protein for degradation by proteasomes.

Uncoupling of NO synthase

  • Nitric oxide (NO*) is an important protective molecule inthe vasculature. Endothelial NO* synthase (eNOS) isresponsible for most of the vascular NO* produced. Thenormal function of eNOS is to oxidize its substrateL-arginine to L-citrulline and NO*. This normal function ofeNOS requires dimerization of the enzyme in the presenceof the substrate L-arginine. This reaction requires anessential co-factor, tetrahydro-L-biopterin (BH4), one ofthe most potent naturally occurring reducing agents.However, if BH4 is diminished due to oxidation, eNOS canpromote the production of the free radical, superoxide(O2*–). If this occurs, the process is referred to as eNOSuncoupling.

Uncoupling protein

  • Uncoupling proteins (UCPs) are proteins that are present in the inner mitochondrial membrane of cells; UCPs dissipate the proton gradient across this membrane. As a result of this action, mitochondrial respiration produces heat instead of adenosine triphosphate (ATP). Heart and skeletal muscle contain two isoforms of UCPs-UCP2 and UCP3. The exact function of these UCPs is not clear, but they may be involved in decreasing reactive oxygen species production by the mitochondria or transporting excess fatty acids out of the mitochondria. The expression of UCPs in the mitochondria is increased in muscle exposed to high fats.

Uncoupling protein

  • Uncoupling proteins (UCP) are proteins that are present inthe inner mitochondrial membrane of cells that dissipatethe proton gradient across this membrane. As a result ofthis action, mitochondrial respiration produces heatinstead of ATP. Heart and skeletal muscle contain twoisoforms of UCPs, UCP2 and UCP3. The exact function ofthese UCP’s is not clear, but they may be involved indecreasing reactive oxygen species production by themitochondria or transporting excess fatty acids out of themitochondria. The expression of UCPs in the mitochondriais increased in muscle exposed to high fats.

Variant angina

  • Variant angina (also known as vasospastic angina) is a form of angina (sensation of chest pain) that occurs at rest in cycles. It is typically caused by a vasospasm, which is an arterial spasm that induces vasoconstriction of smooth muscle cells within the blood vessel wall, leading to myocardial ischemia.

Vascular endothelial growth factor (VEGF)

  • VEGF is a signal protein belonging to the sub-family of the platelet-derived growth factor family. The primary function of VEGF is to stimulate angiogenesis and vasculogenesis. This often occurs when oxygen supply to tissues is limited due to poor blood circulation.

VCAM, ICAM, E-selectin

  • Vascular cell adhesion molecule (VCAM)-1, intracellularadhesion molecule-1 (ICAM-1) and E-Selectin play acentral role in the recruitment of inflammatory cells, andits expression is rapidly induced by proinflammatorycytokines such as TNFαlpha. VCAM-1, ICAM-1 and ESelectionalso play critical roles in many other processes,such as early atherogenesis.

Vectors

  • Vectors is a term commonly used to describe the vehiclefor carrying DNA and protein. For instance, DNA can becontained within an adenoviral vector or a plasmid vector.Proteins such as the b-subunit of Shiga toxin are alsopowerful vectors for carrying peptides into cells.

Viability

  • Viability, at the tissue level, is the ability of parenchymal cells to withstand a pathological insult, and subsequently survive and maintain normal-to-near normal function.

Vinculin

  • Vinculin is a cytoskeletal protein involved in the buildingof the adhesion scaffold. It has been suggested thatvinculin is a key link that connects early adhesion sites tothe actin-driven contractile machinery.

Vitamin D

  • Vitamin D is a fat-soluble secosteroid responsible for intestinal absorption of calcium and phosphate. Vitamin D is not an essential dietary vitamin, as the majority of mammals can synthesize vitamin D endogenously in adequate amounts following sufficient exposure to sunlight. Although vitamin D supplementation has been thought of as having beneficial effects on cardiovascular health, the results of recent studies have proven to be inconclusive and this remains an active area of ongoing research.

Von Hippel-Lindau protein

  • von Hippel-Lindau protein is a tumor-suppressor protein. Ittargets proteins for ubiquitination and degradation. Forinstance, von Hippel-Lindau protein targets HIF-1α forubiquitination and proteasomal degradation.

Warburg effect

  • The Warburg effect is a metabolic phenotype characteristic of rapidly proliferating cells (both normal cells and cancerous cells). This metabolic phenotype is accompanied by distinct alterations in cellular glucose metabolism, specifically an enhanced flux of glucose via glycolysis that results in the subsequent generation and release of lactate, even in the presence of oxygen (i.e., aerobic glycolysis).

Wild-type transthyretin amyloid (WTTA)

  • Wild-type transthyretin amyloid (WTTA) is a disease that arises from the accumulation of wild-type transthyretin (normal version of the protein) in the heart or tendons, and it primarily affects the elderly. Men are affected to a much greater degree than women. As wild-type transthyretin accumulates in the heart, it results in increased myocardial stiffness and wall thickness, precipitating symptoms often including shortness of breath and exercise intolerance.