title: Coronary endothelial cells: a target of ischemia reperfusion and its treatment?
abstract: Ischemia/reperfusion injury of the heart is not limited to cardiomyocytes but also extends to coronary vascular cells, and especially coronary endothelium. Indeed, in different animal models, ischemia followed by reperfusion (but not ischemia alone) markedly decreases endothelium-dependent relaxations of coronary arteries, and especially those induced by nitric oxide (NO), while endothelium-independent responses and smooth muscle responsiveness are usually maintained. Such injury to the endothelium appears to depend on the increased production of oxygen-derived free radicals upon reperfusion, leading to an increased degradation of NO and an acute inflammatory response characterized by an increased adhesion of neutrophils to endothelial cells. Indeed, reperfusion injury to the endothelium may be prevented by free radical scavengers, by prevention of adhesion and/or activation of neutrophils, by exogenous NO supply or increased endogenous production of NO, as well as by ischemic preconditioning. Given the essential role of the endothelium and of NO in the regulation of vasomotor tone, as well as platelet and leukocyte function, it is likely that such changes in coronary endothelial function have important adverse consequences in terms of altered perfusion, and increased risk of vasospasm, but also on the long-term risk of thrombosis and atherosclerosis. Although these coronary endothelial alterations have been essentially evaluated in experimental models and are indeed difficult to assess in the human coronary circulation in the context of myocardial infarction, data obtained in healthy volunteers demonstrate that such post-ischemic alterations of endothelial function may be detected in the peripheral circulation, with underlying molecular mechanisms similar to those demonstrated experimentally. A better understanding of the mechanisms responsible for such endothelial injury may lead to the development of new treatments that protect the endothelium during ischemia and reperfusion, but also possibly in other diseases associated with endothelial dysfunction.
authors.affiliation: Dept of Pharmacology, INSERM U644, Rouen University Medical School, Rouen, France.
authors.forename: K
authors.initials: K
authors.lastname: Laude
authors.forename: V
authors.initials: V
authors.lastname: Richard
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D019194:Ischemic Preconditioning; D017202:Myocardial Ischemia / Q000473:pathology* / Q000628:therapy; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000473:pathology; D018384:Oxidative Stress
chemical_list: D005609:Free Radicals