Number 22, 2004
Endothelial Dysfunction

Endothelial dysfunction

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Graham Jackson
Guys & St Thomas Hospitals, London, UK
Correspondence: Dr Graham Jackson, Cardiovascular Department, St Thomas Hospital, Lambeth Palace Road, London SE1 7EH.
Tel: +44 207 407 5887, fax: +44 207 357 7408, e-mail: graham@jacksonmd.fsnet.co.uk

Endothelial dysfunction is defined as an abnormal endothelial response leading to a reduction in the bioavailability of nitric oxide, and impaired vasodilatation [1]. It has been found to be associated with several disorders of the cardiovascular system, including diabetes, hypertension, hyperlipidemia, and heart failure, and vascular risk factors of cigarette smoking [2,3].
The vascular endothelium acts as a plasmatissue barrier" and has a crucial role in controlling vascular function, with the balance between endothelium-derived vasodilators and vasoconstrictors determining vascular tone and the pathophysiological consequences [4]. In addition, the reduction in nitric oxide bioavailability can adversely affect platelet aggregation, vascular wall inflammation, and smooth muscle cell proliferation.
The clinical consequences of endothelial dysfunction include the development of atherosclerosis, acute coronary syndromes, cardiac failure, and erectile dysfunction. It is no wonder that the vascular endothelium is the focus of so much attention, when it is now recognized that a defect in the nitric oxidecyclic guanosine 3⬲5"-monophosphate system in smooth muscle cells before the development of overt cardiovascular disease in men with erectile dysfunction is an early marker of systemic vascular abnormalities [3,5].
Measures of endothelial dysfunction have been shown to be improved by drugs that benefit cardiovascular morbidity and mortality (angiotensin-converting-enzyme inhibitors in cardiac failure; statins and angiotensin-converting enzyme inhibitors in ischemic heart disease), and erectile dysfunction, heart failure, and diabetes (phosphodiesterase type 5 inhibitors) [6].
As a number of clinical conditions are clearly related to endothelial dysfunction, it becomes increasingly important to develop and validate means of its evaluation, and subsequently to determine whether improving endothelial dysfunction may in turn improve the long-term clinical outcome of conditions such as diabetes and cardiac failure.
The endothelium has a pivotal role through regulating vascular homeostasis. Once believed to be an inert monolayer of cells simply lining blood vessels, the endothelium is now recognized to have the most important role, in local regulation of vessel function. As our understanding of endothelial cell biology has developed  an increasingly rapid awakening  we have come to recognize its worrying potential to give rise to vascular diseases, with the important positive implications that we could use endothelial progenitor cells to promote new vessel formation, and gene therapy to modify endothelial vascular function. There is promise and potential, and it is timely to review what we know and how to look forward  these are exciting times for preventative strategies.
This issue of Heart and Metabolism reviews what is known about endothelial dysfunction, from the basics to its clinical expression and treatment, with an examination of the imaging of coronary endothelial dysfunction by positron emission tomography. Disease mechanisms are open to modification and the next months and (few) years offer important opportunities for endothelial cell research and treatment. Over the past 5 years, we have come to realize that erectile dysfunction is determined by endothelial dysfunction, and that it is modified by phosphodiesterase type 5 inhibitors, which improve endothelial dysfunction by acting within the smooth muscle cell [3,6].
By looking beyond the box of cardiovascular presentations, we may have opportunities to modify disease progression at a very early stage  which is why I feel this issue of Heart and Metabolism will form a template for new ideas in this exciting area.

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REFERENCES

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