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

Heloise Mongue-Din, Ashish S. Patel, Yee H. Looi, David J. Grieve, Narayana Anilkumar, Alexander Sirker, Xuebin Dong, Alison C. Brewer, Min Zhang, Alberto Smith, Ajay M. Shah*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)
40 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)688-698
Number of pages11
JournalJACC: Basic to Translational Science
Volume2
Issue number6
DOIs
Publication statusPublished - 01 Dec 2017
Externally publishedYes

Keywords

  • cardiac
  • infarction
  • ischemia
  • macrophage
  • NADPH oxidase
  • remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Mongue-Din, H., Patel, A. S., Looi, Y. H., Grieve, D. J., Anilkumar, N., Sirker, A., Dong, X., Brewer, A. C., Zhang, M., Smith, 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