Atherosclerosis-associated endothelial dysfunction.
The endothelium plays a crucial role in the process of atherosclerotic disease by its regulatory functions on the vasculature, such as control of vasomotor tone, local hemostasis and proliferative processes. Dysfunction of endothelial vasoreactivity contributes to reduced myocardial blood supply and, therefore, might promote myocardial ischemia. To control vasomotor tone, the endothelium releases a variety of substances such as prostacyclin, hyperpolarizing factor, endothelin and, most importantly, nitric oxide (NO). Endothelium-dependent vasodilation is impaired in patients with environmental or genetic risk factors for atherosclerotic disease, such as hypercholesterolemia, mainly due to increased oxidative stress produced by superoxide anions, which rapidly inactivate nitric oxide. Experimentally, an imbalance between nitric oxide and superoxide anions towards reduced nitric oxide bioavailability enhances migration of monocytes into the vessel wall and proliferation of smooth muscle cells. These oxidative processes, resembling a chronic inflammatory process, extending to the vessel wall, contribute to plaque architecture, e.g., by destabilization of fibrous caps. Indeed, long-term follow-up of patients with endothelial dysfunction demonstrated that impaired endothelium-dependent vasodilation is associated with increased cardiovascular event rates. Recent clinical data supported the role of endothelial dysfunction in patients with acute coronary syndrome and demonstrated a relation with elevated C-reactive protein levels, an unspecific marker of inflammation. Taken together, assessment of coronary endothelial vasoreactivity may serve as an index integrating the overall stress imposed by risk factors on the arterial wall and provides pivotal information, both as a diagnostic and prognostic tool in patients at risk for coronary heart disease.
Schächinger
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Medizinische Klinik IV, Kardiologie J. W. Goethe Universität Frankfurt Theodor-Stern-Kai 7 60590 Frankfurt, Germany. schaechinger@em.uni-frankfurt.de
Zeiher
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AM
D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology; D001794:Blood Pressure; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology; D004562:Electrocardiography; D015716:Electrocardiography, Ambulatory; D004730:Endothelium, Vascular / Q000503:physiopathology*; D015444:Exercise; D005500:Follow-Up Studies; D006339:Heart Rate; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D008833:Microcirculation / Q000502:physiology; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D014661:Vasoconstriction; D014664:Vasodilation; D014666:Vasomotor System / Q000502:physiology
D009569:Nitric Oxide