Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury

被引：134

作者：

Braunersreuther, Vincent ^{[1
,2
]}

Montecucco, Fabrizio ^{[1
,3
]}

Ashri, Mohammed ^{[1
]}

Pelli, Graziano ^{[1
]}

Galan, Katia ^{[1
]}

Frias, Miguel ^{[4
]}

Burger, Fabienne ^{[1
]}

Gomez Quindere, Ana Luiza ^{[5
]}

Montessuit, Christophe ^{[1
]}

Krause, Karl-Heinz ^{[6
]}

Mach, Francois ^{[1
]}

Jaquet, Vincent ^{[6
]}

机构：

[1] Fdn Med Res, Univ Hosp, Dept Med, Div Cardiol, CH-1211 Geneva, Switzerland

[2] Univ Hosp Geneva, Dept Genet Med & Labs, Div Clin Pathol, CH-1211 Geneva, Switzerland

[3] Univ Geneva, Dept Internal Med, Clin Internal Med 1, I-16132 Genoa, Italy

[4] Univ Hosp Geneva, Serv Endocrinol Diabetol & Nutr, CH-1211 Geneva 14, Switzerland

[5] Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil

[6] Univ Geneva, Ctr Med Univ, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2013年 / 64卷

基金：

瑞士国家科学基金会;

关键词：

NADPH oxidase; NOX; Myocardial ischemia; Reperfusion injury; ROS; FREE-RADICAL GENERATION; REACTIVE OXYGEN; REPERFUSION INJURY; DOWN-REGULATION; EBSELEN; FAMILY; PEROXIDASE; PHYSIOLOGY; ARTHRITIS; OXIDATION;

D O I：

10.1016/j.yjmcc.2013.09.007

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Myocardial reperfusion injury is mediated by several processes including increase of reactive oxygen species (ROS). The aim of the study is to identify potential sources of ROS contributing to myocardial ischemia-reperfusion injury. For this purpose, we investigated myocardial ischemia/reperfusion pathology in mice deficient in various NADPH oxidase isoforms (Nox1, Nox2, Nox4, as well as Nox1/2 double knockout). Following 30 min of ischemia and 24 h of reperfusion, a significant decrease in the size of myocardial infarct was observed in Nox1-, Nox2- and Nox1/Nox2-, but not in Nox4-deficient mice. However, no protection was observed in a model of chronic ischemia, suggesting that NOX1 and NOX2-mediated oxidative damage occurs during reperfusion. Cardioprotective effect of Nox1 and Nox2 deficiencies was associated with decrease of neutrophil invasion, but, on the other hand an improved reperfusion injury was also observed in isolated perfused hearts (Langendorff model) suggesting that inflammatory cells were not the major source of oxidative damage. A decrease in global post-reperfusion oxidative stress was clearly detected in Nox2-, but not in Nox1-deficient hearts. Analysis of key signaling pathways during reperfusion suggests distinct cardioprotective patterns: increased phosphorylation was seen for Ala and Erk in Nox1-deficient mice and for Stat3 and Erk in Nox2-deficient mice. Consequently, NOX1 and NOX2 represent interesting drug targets for controlling reperfusion damage associated with revascularization in coronary disease. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：99 / 107

页数：9

共 40 条

[1]

Gp91phox contributes to the development of experimental inflammatory bowel disease [J].