Information de reference pour ce titreAccession Number: | 00004686-199806010-00029.
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Author: | Murohara, Toyoaki; Asahara, Takayuki; Silver, Marcy; Bauters, Christophe; Masuda, Haruchika; Kalka, Christoph; Kearney, Marianne; Chen, Donghui; Chen, Dongfen; Symes, James F.; Fishman, Mark C.; Huang, Paul L.; Isner, Jeffrey M.
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Institution: | (Murohara, Asahara, Silver, Bauters, Masuda, Kalka, Kearney, Chen, Chen, Symes, Isner) Department of Medicine (Cardiology) and Department of Cardiothoracic Surgery and Biomedical Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135; and (Fishman, Huang) Cardiovascular Research Center and Cardiac Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02111. T. Murohara and T. Asahara contributed equally to this work. Address correspondence to Jeffrey M. Isner, St. Elizabeth's Medical Center, 736 Cambridge Street, Boston, MA 02135. Phone: 617-789-2392. FAX: 617-779-6362. E-mail: [email protected]. Received for publication 21 August 1997 and accepted in revised form 1 April 1998.
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Title: | Nitric Oxide Synthase Modulates Angiogenesis in Response to Tissue Ischemia.[Miscellaneous Article]
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Source: | Journal of Clinical Investigation. 101(11):2567-2578, June 1, 1998.
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Abstract: | We tested the hypothesis that endothelial nitric oxide synthase (eNOS) modulates angiogenesis in two animal models in which therapeutic angiogenesis has been characterized as a compensatory response to tissue ischemia.We first administered L-arginine, previously shown to augment endogenous production of NO, to normal rabbits with operatively induced hindlimb ischemia. Angiogenesis in the ischemic hindlimb was significantly improved by dietary supplementation with L-arginine, compared to placebo-treated controls; angiographically evident vascularity in the ischemic limb, hemodynamic indices of limb perfusion, capillary density, and vasomotor reactivity in the collateral vessel-dependent ischemic limb were all improved by oral L-arginine supplementation. A murine model of operatively induced hindlimb ischemia was used to investigate the impact of targeted disruption of the gene encoding for ENOS on angiogenesis. Angiogenesis in the ischemic hindlimb was significantly impaired in eNOS (-/-) mice versus wild-type controls evaluated by either laser Doppler flow analysis or capillary density measurement. Imparied angiogenesis in eNOS-/- mice was not improved by administration of vascular endothelial growth factor (VEGF), suggesting that eNOS acts downstream from VEGF. Thus, (a) eNOS is a downstream mediator for in vivo angiogenesis, and (b) promoting eNOS activity by L-arginine supplementation accelerates in vivo angiogenesis. These findings suggest that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation constitutes a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction. (J. Clin. Invest. 1998. 101:2567-2578.)
Copyright (C) 1998 The American Society for Clinical Investigation, Inc.
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Language: | English.
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Document Type: | Cellular, Transport And Organ Physiology.
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Journal Subset: | Clinical Medicine. Life Sciences.
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ISSN: | 0021-9738
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NLM Journal Code: | hs7, 7802877
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