Hypoxia Induces M2 Macrophages to Express VSIG4 and Mediate Cardiac Fibrosis After Myocardial Infarction

Abstract

M2 macrophage-mediated tissue repair plays an important role in acute myocardial infarction (AMI). Additionally, VSIG4, which is mainly expressed on tissue-resident and M2 macrophages, is crucial for the regulation of immune homeostasis; however, its effects on AMI remain unknown. In this study, we aimed to investigate the functional significance of VSIG4 in AMI using <i>VSIG4</i> knockout and adoptive bone marrow transfer chimeric models. We also determined the function of cardiac fibroblasts (CFs) through gain- or loss-of-function experiments. We showed that VSIG4 promotes scar formation and orchestrates the myocardial inflammatory response after AMI, while also promoting TGF-β1 and IL-10. Moreover, we revealed that hypoxia promotes VSIG4 expression in cultured bone marrow M2 macrophages, ultimately leading to the conversion of CFs to myofibroblasts. Our results reveal a crucial role for VSIG4 in the process of AMI in mice and provide a potential immunomodulatory therapeutic avenue for fibrosis repair after AMI.