title: Involvement of Nox2 NADPH oxidase in adverse cardiac remodeling after myocardial infarction.
abstract: Oxidative stress plays an important role in the development of cardiac remodeling after myocardial infarction (MI), but the sources of oxidative stress remain unclear. We investigated the role of Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase in the development of cardiac remodeling after MI. Adult Nox2(-/-) and matched wild-type (WT) mice were subjected to coronary artery ligation and studied 4 weeks later. Infarct size after MI was similar in Nox2(-/-) and WT mice. Nox2(-/-) mice exhibited significantly less left ventricular (LV) cavity dilatation and dysfunction after MI than WT mice (eg, echocardiographic LV end-diastolic volume: 75.7+/-5.8 versus 112.4+/-12.3 microL; ejection fraction: 41.6+/-3.7 versus 32.9+/-3.2%; both P<0.05). Similarly, in vivo LV systolic and diastolic functions were better preserved in Nox2(-/-) than WT mice (eg, LV dP/dt(max): 7969+/-385 versus 5746+/-234 mm Hg/s; LV end-diastolic pressure: 12.2+/-1.3 versus 18.0+/-1.8 mm Hg; both P<0.05). Nox2(-/-) mice exhibited less cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis; reduced increases in expression of connective tissue growth factor and procollagen 1 mRNA; and smaller increases in myocardial matrix metalloproteinase-2 activity than WT mice. These data suggest that the Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase contributes significantly to the processes underlying adverse cardiac remodeling and contractile dysfunction post-MI.
authors.affiliation: Department of Cardiology, King's College London School of Medicine, James Black Centre, 125 Coldharbour Ln, London SE5 9NU, United Kingdom.
authors.forename: Yee H
authors.initials: YH
authors.lastname: Looi
authors.forename: David J
authors.initials: DJ
authors.lastname: Grieve
authors.forename: Anjana
authors.initials: A
authors.lastname: Siva
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Walker
authors.forename: Narayana
authors.initials: N
authors.lastname: Anilkumar
authors.forename: Alison C
authors.initials: AC
authors.lastname: Cave
authors.forename: Michael
authors.initials: M
authors.lastname: Marber
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Monaghan
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000818:Animals; D017209:Apoptosis; D006328:Cardiac Catheterization; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism; D004452:Echocardiography; D005355:Fibrosis; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D020778:Matrix Metalloproteinase 2