title: Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction.
abstract: Increased reactive oxygen species (ROS) production is involved in the process of adverse cardiac remodeling and development of heart failure after myocardial infarction (MI). NADPH oxidase-2 (Nox2) is a major ROS source within the heart and its activity increases after MI. Furthermore, genetic deletion of Nox2 is protective against post-MI cardiac remodeling. Nox2 levels may increase both in cardiomyocytes and endothelial cells and recent studies indicate cell-specific effects of Nox2, but it is not known which of these cell types is important in post-MI remodeling.
  
  
  
  We have generated transgenic mouse models in which Nox2 expression is targeted either to cardiomyocytes (cardio-Nox2TG) or endothelial cells (endo-Nox2TG). We here studied the response of cardio-Nox2TG mice, endo-Nox2TG mice and matched wild-type littermates (WT) to MI induced by permanent left coronary artery ligation up to 4weeks. Initial infarct size assessed by magnetic resonance imaging (MRI) and cardiac dysfunction were similar among groups. Cardiomyocyte hypertrophy and interstitial fibrosis were augmented in cardio-Nox2TG compared to WT after MI and post-MI survival tended to be worse whereas endo-Nox2TG mice showed no significant difference compared to WT.
  
  
  
  These results indicate that cardiomyocyte rather than endothelial cell Nox2 may have the more important role in post-MI remodeling.
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sirker
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Colin E
authors.initials: CE
authors.lastname: Murdoch
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Protti
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Greta J
authors.initials: GJ
authors.lastname: Sawyer
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Celio X C
authors.initials: CX
authors.lastname: Santos
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Brewer
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: King's College London British Heart Foundation Centre of Excellence, Cardiovascular Division, London, UK. Electronic address: ajay.shah@kcl.ac.uk.
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D018487:Ventricular Dysfunction, Left; D020257:Ventricular Remodeling
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: Cardiac remodeling; Heart failure; Myocardial infarction; NADPH oxidase; Reactive oxygen species