Endothelial dysfunction: the first step toward coronary arteriosclerosis.
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.
Vanhoutte
Paul M
PM
Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. vanhoutt@hku.hk
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
D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11