Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders

被引：109

作者：

Gielis, Jan F. ^{[2
]}

Lin, Judy Y. ^{[1
]}

Wingler, Kirstin ^{[3
]}

Van Schil, Paul E. Y. ^{[2
]}

Schmidt, Harald H. ^{[3
]}

Moens, An L. ^{[1
]}

机构：

[1] Maastricht Univ Med Ctr, Dept Cardiol, Cardiovasc Res Inst Maastricht, NL-6202 AZ Maastricht, Netherlands

[2] Univ Antwerp, Dept Vasc & Thorac Surg, B-2020 Antwerp, Belgium

[3] Maastricht Univ Med Ctr, Dept Pharmacol, Cardiovasc Res Inst Maastricht, NL-6202 AZ Maastricht, Netherlands

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2011年 / 50卷 / 07期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

eNOS uncoupling; Superoxide; Tetrahydrobiopterin; eNOS modulators; Cardioprotection; Free radicals; NITRIC-OXIDE SYNTHASE; ENDOTHELIUM-DEPENDENT VASODILATION; VASCULAR SUPEROXIDE-PRODUCTION; GTP CYCLOHYDROLASE-I; L-ARGININE; FOLIC-ACID; MYOCARDIAL-INFARCTION; REPERFUSION INJURY; OXIDATIVE STRESS; TRANSGENIC MICE;

D O I：

10.1016/j.freeradbiomed.2010.12.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS) oxidizes L-arginine to L-citrulline and nitric oxide (NO), which acutely vasodilates blood vessels and inhibits platelet aggregation. Chronically, eNOS has a major role in the regulation of blood pressure and prevention of atherosclerosis by decreasing leukocyte adhesion and smooth muscle proliferation. However, a disturbed vascular redox balance result:; in eNOS damage and uncoupling of oxygen activation from L-arginine conversion. Uncoupled eNOS monomerizes and generates reactive oxygen species (ROS) rather than NO. Indeed, eNOS uncoupling has been suggested as one of the main pathomechanisms in a broad range of cardiovascular and pulmonary disorders such as atherosclerosis, ventricular remodeling, and pulmonary hypertension. Therefore, modulating uncoupled eNOS, in particular eNOS-dependent ROS generation, is an attractive therapeutic approach to preventing and/or treating cardiopulmonary disorders, including protective effects during cardiothoracic surgery. This review provides a comprehensive overview of the pathogenetic role of uncoupled eNOS in both cardiovascular and pulmonary disorders. In addition, the related therapeutic possibilities such as supplementation with the eNOS substrate L-arginine, volatile NO, and direct NO donors as well as eNOS modulators such as the eNOS cofactor tetrahydrobiopterin and folic acid are discussed in detail. (C) 2010 Published by Elsevier Inc.

引用

页码：765 / 776

页数：12

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