Neuronal nitric oxide synthase as a novel anti-atherogenic factor.
Nitric oxide (NO) has multiple important actions that contribute to the maintenance of vascular homeostasis. NO is synthesized by three different isoforms of NO synthase (NOS), all of which have been reported to be expressed in human atherosclerotic vascular lesions. Although the regulatory roles of endothelial NOS (eNOS) and inducible NOS (iNOS) on the development of atherosclerosis have been described, little is known about the role of neuronal NOS (nNOS). Recent studies have demonstrated that nNOS also exerts important vasculoprotective effects in vivo. In a carotid artery ligation model, nNOS-knockout mice exhibited accelerated neointimal formation and constrictive vascular remodeling caused by blood flow disruption. In a rat balloon injury model, the selective inhibition of nNOS activity potently enhanced vasoconstrictor responses to a variety of calcium-mobilizing stimuli, and exacerbated neointimal formation. Moreover, in apolipoprotein E-knockout mice, deficiency of nNOS induced progression of aortic vascular lesion formation. In these models, nNOS was up-regulated in vascular lesions, and was predominantly expressed in the neointima and medial smooth muscle cells. These results provide the first direct evidence that nNOS plays important roles in suppressing arteriosclerotic vascular lesion formation. Thus, nNOS could be regarded as a novel anti-atherogenic factor.
Tsutsui
Masato
M
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Fukuoka 807-8555, Japan. mt2498@med.uoeh-u.ac.jp
D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology*; D002417:Cattle; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D051381:Rats
D009419:Nerve Tissue Proteins; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat