doi: 10.1161/01.CIR.0000099580.72044.83
(Circulation. 2003;108:2060.)
© 2003 American Heart Association, Inc.
Mini-Review: Expert Opinions |
Endothelial Dysfunction
From St Luke’s Episcopal Hospital/Texas Heart Institute (J.T.W.), Houston, Tex, and the Carl and Edyth Lindner Center for Research and Education (D.J.K.), Ohio Heart Health Center, Cincinnati, Ohio.
Correspondence to James T. Willerson, MD, SLEH/THI, 6720 Bertner Ave, Room B 524, Houston, TX 77030. E-mail suzy.lanier{at}uth.tmc.edu
Drs Ganz and Vita1 and Verma, Buchanan, and Anderson2 have presented persuasive evidence that endothelial function is dynamically regulated and that the endothelium’s vasodilator, antiinflammatory, and antithrombotic properties are markedly diminished by a variety of injuries, including atherosclerosis, hypertension, diabetes, inflammation, and aging. Moreover, they identify several recent studies that provide evidence that endothelial dysfunction in both coronary and peripheral arteries precedes the development of the clinical consequences of atherothrombosis. Testing of endothelial function still rests largely in the administration of an endothelium-dependent vasodilator, such as acetylcholine, or in evaluating brief periods of occlusion of an artery followed by functional assessment of that artery, which is vasodilation when normal and failure of vasodilation or vasoconstriction when abnormal. Quantitative coronary arteriography has been used in the past to measure coronary vasomotor responses, and more recently, ultrasound has been used as a noninvasive measurement of endothelial function, especially when examining brachial arteries.
However, what is missing from these assessments is an evaluation of other aspects of endothelial function, including antithrombotic, metabolic, and antiinflammatory properties. It is likely that subtle or early injury to the endothelium alters only one or two of the endothelial functional properties, whereas more extensive injury alters most or all of endothelial function, hastening the development of atherothrombosis and progressive vascular disease. This is an area where development needs to occur so that one might be able to assess a broader array of endothelial functional properties, anticipating greater predictive ability with regard to acute coronary artery syndromes, cerebrovascular accidents, and/or complications of peripheral vascular disease. It is also necessary to develop improved noninvasive means of evaluating endothelial function in coronary arteries, cerebral arteries, and peripheral arteries that are not amenable to evaluation by noninvasive ultrasound at present. Future developments in these areas should allow broader interrogation of arteries in the human body and provide even greater insight into arteries at risk for atherothrombosis and its consequences.
Drs Verma, Buchanan, and Anderson2 seek to identify one or more biomarker(s) of vascular disease that would serve as surrogates for endothelial dysfunction. They suggest C-reactive protein. However, the studies available thus far do not provide compelling evidence that alterations in any biomarker correlate specifically with endothelial dysfunction. One anticipates finding abnormal endothelial function in individuals with very elevated C-reactive protein as a consequence of acute coronary syndromes, cerebrovascular accidents, marked hyperlipidemia, etc. Future studies may indeed provide more evidence of selective or generalized endothelial dysfunction with elevations in C-reactive protein (or some other biomarkers), but this will still not provide direct insight into the arterial system that is involved.
Thus, there is work to do in developing improved noninvasive imaging that can evaluate endothelial function in arteries throughout the body and in identifying biomarkers with sensitivity and specificity for detection of early and progressive endothelial dysfunction. Finally, information that establishes the protective effect of selected interventions that reverse inflammation, correct hyperlipidemia and systemic arterial hypertension, control blood sugars in diabetic patients, and reverse endothelial dysfunction in altering progressive atherothrombosis and its consequences is also needed. Nevertheless, endothelial functional testing broadly identifying dysfunction and its potential correction with medical intervention may prove to be one of the very important advances in noninvasive diagnosis and predicting prognosis in patients with vascular disease, once improved noninvasive imaging techniques are developed and further evidence is provided that reversal of endothelial dysfunction protects against progression of vascular disease.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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 Top References |
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1. Ganz P, Vita JA. Testing endothelial vasomotor function: nitric oxide, a multipotent molecule. Circulation. 2003; 108: 2049–2053.
2. Verma S, Buchanan M, Anderson TJ. Endothelial function testing as a biomarker of vascular disease. Circulation. 2003; 108: 2054–2059.
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