Author + information
- Received January 30, 2017
- Revision received May 23, 2017
- Accepted June 20, 2017
- Published online December 25, 2017.
- Heloise Mongue-Din, PharmD, PhDa,
- Ashish S. Patel, PhDb,
- Yee H. Looi, PhDa,
- David J. Grieve, PhDa,
- Narayana Anilkumar, PhDa,
- Alexander Sirker, PhDa,
- Xuebin Dong, MD, PhDa,
- Alison C. Brewer, PhDa,
- Min Zhang, MD, PhDa,
- Alberto Smith, PhDb and
- Ajay M. Shah, MDa,∗ ()
- aKing's College London British Heart Foundation Centre, Cardiovascular Division, James Black Centre, London, United Kingdom
- bKing's College London British Heart Foundation Centre, Cardiovascular Division, Academic Department of Vascular Surgery, St. Thomas' Hospital, London, United Kingdom
- ↵∗Address for correspondence:
Prof. Ajay M. Shah, Cardiovascular Division, King's College London, The James Black Centre, 125 Coldharbour Lane, London SE5 9NU, United Kingdom.
• 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.
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.
Supported by the British Heart Foundation and the Department of Health via a National Institute for Health Research Biomedical Research Centre award to Guy’s & St. Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received January 30, 2017.
- Revision received May 23, 2017.
- Accepted June 20, 2017.
- 2017 The Authors