title: Endothelial dysfunction: the first step toward coronary arteriosclerosis.
abstract: The endothelium causes relaxations of the underlying vascular smooth muscle, by releasing nitric oxide (NO). The endothelial cells also can evoke hyperpolarization of the vascular smooth muscle cells (endothelium-dependent hyperpolarizations, endothelium-derived hyperpolarizing factors-mediated responses). Endothelium-dependent relaxations involve both pertussis toxin-sensitive Gi and pertussis toxin-insensitive Gq coupling proteins. The endothelial release of NO is reduced in diabetes and hypertension. Arteries covered with regenerated endothelium lose the pertussis-toxin sensitive pathway for NO-release. This dysfunction favors vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. Endothelial cells also release endothelium-derived contracting factors (EDCF). Most endothelium-dependent contractions are mediated by vasoconstrictor prostanoids (endoperoxides and prostacyclin), which activate thromboxane-prostanoid (TP)-receptors of the underlying vascular smooth muscle cells. EDCF-mediated responses are augmented by aging, hypertension and diabetes. Thus, endothelial dysfunction is the first step toward coronary arteriosclerosis.
authors.affiliation: Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. vanhoutt@hku.hk
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000818:Animals; D016764:Cell Polarity; D003324:Coronary Artery Disease / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D003329:Coronary Vasospasm / Q000378:metabolism / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000378:metabolism
chemical_list: D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11