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

Braunersreuther, Vincent; Montecucco, Fabrizio; Asrih, Mohamed; Ashri, Mohammed; Pelli, Graziano; Galan, Katia; Frias, Miguel; Burger, Fabienne; Quinderé, Ana Luíza Gomez; Montessuit, Christophe Albert; Krause, Karl-Heinz; Mach, François; Jaquet, Vincent

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Title		Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury
Authors		Braunersreuther, Vincent Montecucco, Fabrizio Asrih, Mohamed Ashri, Mohammed Pelli, Graziano Galan, Katia Frias, Miguel Burger, Fabienne Quinderé, Ana Luíza Gomez Montessuit, Christophe Albert Krause, Karl-Heinz Mach, François Jaquet, Vincent show all authors [1 - 13]
Published in		Journal of Molecular and Cellular Cardiology. 2013, vol. 64, p. 99-107
Abstract		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 30min of ischemia and 24h 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 Akt 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.
Keywords		Animals — Cytokines/blood — Disease Models, Animal — Isoenzymes — Macrophages/pathology — Male — Membrane Glycoproteins/genetics/metabolism — Mice — Mice, Knockout — Myocardial Reperfusion Injury/genetics/metabolism/pathology/prevention & control — Myocardium/metabolism/pathology — NADH, NADPH Oxidoreductases/genetics/metabolism — NADPH Oxidase/genetics/metabolism — Neutrophil Infiltration/genetics — Phosphorylation — Reactive Oxygen Species/metabolism — Signal Transduction
Identifiers		DOI: 10.1016/j.yjmcc.2013.09.007 PMID: 24051369
Full text		Article (Published version) (849 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research groups		Ophtalmologie expérimentale (925) Radicaux libres et cellules souches embryonnaires (60) Biologie du myocarde (22)
Citation (ISO format)		BRAUNERSREUTHER, Vincent et al. Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury. In: Journal of Molecular and Cellular Cardiology, 2013, vol. 64, p. 99-107. https://archive-ouverte.unige.ch/unige:74909