HIMF deletion ameliorates acute myocardial ischemic injury by promoting macrophage transformation to reparative subtype

Author:

Li Yanjiao,Dong Min,Wang Qing,Kumar Santosh,Zhang Rui,Cheng Wanwen,Xiang Jiaqing,Wang Gang,Ouyang Kunfu,Zhou Ruxing,Xie Yaohong,Lu Yishen,Yi Jing,Duan Haixia,Liu JieORCID

Abstract

AbstractAppropriately manipulating macrophage M1/M2 phenotypic transition is a promising therapeutic strategy for tissue repair after myocardial infarction (MI). Here we showed that gene ablation of hypoxia-induced mitogenic factor (HIMF) in mice (Himf−/− and HIMFflox/flox;Lyz2-Cre) attenuated M1 macrophage-dominated inflammatory response and promoted M2 macrophage accumulation in infarcted hearts. This in turn reduced myocardial infarct size and improved cardiac function after MI. Correspondingly, expression of HIMF in macrophages induced expression of pro-inflammatory cytokines; the culturing medium of HIMF-overexpressing macrophages impaired the cardiac fibroblast viability and function. Furthermore, macrophage HIMF was found to up-regulate C/EBP-homologous protein (CHOP) expression, which exaggerated the release of pro-inflammatory cytokines via activating signal transducer of activator of transcription 1 (STAT1) and 3 (STAT3) signaling. Together these data suggested that HIMF promotes M1-type and prohibits M2-type macrophage polarization by activating the CHOP–STAT1/STAT3 signaling pathway to negatively regulate myocardial repair. HIMF might thus constitute a novel target to treat MI.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Basic Research Foundation of Shenzhen

Publisher

Springer Science and Business Media LLC

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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