The reactive oxygen species–generating enzyme NADPH oxidase 4 (Nox4) is up-regulated in the heart after myocardial infarction (MI). Mice with cardiomyocyte-targeted Nox4 overexpression (TG) displayed increased macrophages in the heart at baseline, with skewing toward an M2 phenotype compared with wild-type controls (WT). After MI, TG mice had a higher proportion of M2 macrophages along with higher survival, decreased cardiac remodeling, and better contractile function than wild-type mice. The post-MI increase in cardiac matrix metalloproteinase–2 activity was substantially blunted in TG mice. These results indicate that cardiomyocyte Nox4 modulates macrophage polarization toward an M2 phenotype, resulting in improved post-MI survival and remodeling, likely through the attenuation of cardiac matrix metalloproteinase–2 activity.
Mongue-Din, H., Patel, A. S., Looi, Y. H., Grieve, D. J., Anilkumar, N., Sirker, A., … Shah, A. M. (2017). NADPH Oxidase-4 Driven Cardiac Macrophage Polarization Protects Against Myocardial Infarction–Induced Remodeling. JACC: Basic to Translational Science, 2(6), 688–698. https://doi.org/10.1016/j.jacbts.2017.06.006