Cell-specific effects of Nox2 on the acute and chronic response to myocardial infarction. (September 2016) - Sirker, Alexander
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 4 weeks. 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. Highlights: ROS contribute to adverse cardiac remodeling after myocardial infarction (MI). Nox2 is a major cardiac ROS source but with cell-specific effects. Increased Nox2 in cardiomyocytes augments hypertrophy and fibrosis post-MI. Increased Nox2 in endothelium has no significant effect on cardiac remodeling after MI. C ardiomyocyte Nox2 may have the more important role in post-MI remodeling.