title: Nitric oxide insufficiency and atherothrombosis.
abstract: Nitric oxide (NO) is a structurally simple compound that participates in a wide range of biological reactions to maintain normal endothelial function and an antithrombotic intravascular milieu. Among its principal effects are the regulation of vascular tone, vascular smooth muscle cell proliferation, endothelial-leukocyte interactions, and the antiplatelet effects of the endothelium. Impaired NO bioavailability represents the central feature of endothelial dysfunction, the earliest stage in the atherosclerotic process, and also contributes to the pathogenesis of acute vascular syndromes by predisposing to intravascular thrombosis. The causes of NO insufficiency can be grouped into two fundamental mechanisms: inadequate synthesis and increased inactivation of NO. Polymorphisms in the endothelial NO synthase gene and decreased substrate or cofactor availability for this enzyme are the main mechanisms that compromise the synthesis of NO. Inactivation of NO occurs mainly through its interaction with reactive oxygen species and can be favored by a deficiency of antioxidant enzymes such as glutathione peroxidase. In this review, we present an overview of NO synthesis and biological chemistry, discuss the mechanisms of action of NO in regulating endothelial and platelet function, and explore the causes of NO insufficiency, as well as the evidence linking these causes to the pathophysiology of endothelial dysfunction and atherothrombosis.
authors.affiliation: Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, 715 Albany Street, W507, Boston, MA 02118, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Voetsch
authors.forename: Richard C
authors.initials: RC
authors.lastname: Jin
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005979:Glutathione Peroxidase / Q000172:deficiency; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D009569:Nitric Oxide; D005979:Glutathione Peroxidase; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III