Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction

Alexander Sirker, Colin E. Murdoch, Andrea Protti, Greta J. Sawyer, Celio X.C. Santos, Daniel Martin, Xiaohong Zhang, Alison C. Brewer, Min Zhang, Ajay M. Shah

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    Abstract

    Background: 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.
    Methods and results: 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.
    Conclusions: These results indicate that cardiomyocyte rather than endothelial cell Nox2 may have the more important role in post-MI remodeling.
    Original languageEnglish
    Pages (from-to)11-17
    Number of pages7
    JournalJournal of Molecular and Cellular Cardiology
    Volume98
    Early online date7 Jul 2016
    DOIs
    Publication statusPublished - Sept 2016

    Keywords

    • NADPH oxidase
    • myocardial infarction
    • heart failure
    • cardiac remodeling
    • reactive oxygen species

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