title: The two faces of endothelial nitric oxide synthase in the pathophysiology of atherosclerosis.
abstract: In the endothelium, nitric oxide (NO) is constitutively generated from the conversion of L-arginine to L-citrullin by the enzymatic action of endothelial NO synthase (eNOS). An impairment of endothelium-dependent relaxation (EDR) is present in atherosclerotic vessels even before vascular structural changes occur, and represents the reduced eNOS-derived NO activity. Because of its multiple biological actions, NO from eNOS is believed to act as an anti-atherogenic molecule. On the other hand, there is increased production of superoxide in atherosclerotic vessels, which promotes atherogenesis. Recently it is revealed that eNOS becomes dysfunctional and produces superoxide rather than NO under various pathological conditions in which tissue levels of BH4 are reduced. The pathological role of dysfunctional eNOS has attracted attentions in vascular disorders including atherosclerosis, in which abnormal pteridine metabolisms in vascular tissue including decreased BH4 levels and increased BH2 levels have been demonstrated. The presence of dysfunctional eNOS may not only impair EDR but also accelerate lesion formation in atherosclerotic vessels. This review focuses on two faces of eNOS as both an NO- as well as superoxide-producing enzyme depending on tissue pteridine metabolisms in the pathophysiology of atherosclerosis.
authors.affiliation: Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. kawashim@med.kobe-u.ac.jp
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology / Q000503:physiopathology*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D001708:Biopterins; D019001:Nitric Oxide Synthase; C003402:sapropterin