NADPH Oxidase-4 Driven Cardiac Macrophage Polarization Protects Against Myocardial Infarction-Induced Remodeling.

•The reactive oxygen species–generating enzyme NADPH oxidase 4 (Nox4) is up-regulated in the heart after myocardial infarction.•Mice with cardiomyocyte-targeted overexpression of Nox4 display an increase in macrophages in the heart, with skewing of polarization toward an M2 phenotype.•After myocardial infarction, Nox4-induced skewing of macrophage polarization toward an M2 phenotype is accompanied by a higher survival, decreased cardiac remodeling, and improved contractile function.•The protective effects of cardiomyocyte Nox4 may, in part, involve the attenuation of cardiac matrix metalloproteinase–2 activity.