NADPH Oxidase-4 Driven Cardiac Macrophage Polarization Protects Against Myocardial Infarction-Induced Remodeling.
JACC Basic Transl Sci
; 2(6): 688-698, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-29445778
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.
I/R, ischemia/reperfusion; IL, interleukin; LAD, left anterior descending coronary artery; LV, left ventricular; MI, myocardial infarction; MMP, matrix metalloproteinase; NADPH oxidase; NF-κB, nuclear factorκB; Nox, NADPH oxidase; TG, transgenic; WT, wild-type; cardiac; infarction; ischemia; mRNA, messenger ribonucleic acid; macrophage; remodeling
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
JACC Basic Transl Sci
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido