title: Coronary endothelial dysfunction after ischemia and reperfusion: a new therapeutic target?
abstract: Although cardiac ischemia is usually characterized as a disease of the myocyte, it is clear that the vasculature, and especially endothelial cells, is also a major target of this pathology. Indeed, using a rat model of ischemia/reperfusion, we were able to detect severe endothelial dysfunction (assessed as a decreased response to acetylcholine) after acute or chronic reperfusion. Given the essential role of the endothelium in the regulation of vascular tone, as well as platelet and leukocyte function, such a severe dysfunction could lead to an increased risk of vasospasm, thrombosis and accelerated atherosclerosis. This dysfunction can be prevented by free radical scavengers and by exogenous nitric oxide. Endothelial dysfunction can also be prevented by preconditioning with brief periods of intermittent ischemia, thus extending to coronary endothelial cells the concept of endogenous protection previously described at the myocyte level. Experiments performed on cultured cells showed that the endothelial protection induced by free radical scavengers or by preconditioning was due to a lesser expression of endothelial adhesion molecules such as intercellular adhesion molecule-1, leading to a lesser adhesion of neutrophils to endothelial cells. Identification of the mechanisms of this protection may lead to the development of new strategies aimed at protecting the vasculature in ischemic heart diseases.
authors.affiliation: Faculté de Médecine-Pharmacie de Rouen, Rouen, France.
authors.forename: K
authors.initials: K
authors.lastname: Laude
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
authors.forename: V
authors.initials: V
authors.lastname: Richard
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine