2. Academic Validation
  3. HIMF deletion ameliorates acute myocardial ischemic injury by promoting macrophage transformation to reparative subtype

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

  • Basic Res Cardiol. 2021 Apr 23;116(1):30. doi: 10.1007/s00395-021-00867-7.
Yanjiao Li  # 1 2,  Min Dong  # 1 2,  Qing Wang 1 2,  Santosh Kumar 1 2,  Rui Zhang 1 2,  Wanwen Cheng 1 2,  Jiaqing Xiang 1 2,  Gang Wang 1 2,  Kunfu Ouyang 3,  Ruxing Zhou 1 2,  Yaohong Xie 1 2,  Yishen Lu 1 2,  Jing Yi 1 2,  Haixia Duan 1 2,  Jie Liu 4 5
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Pathophysiology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • 2 Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University Health Science Center, Shenzhen, 518060, China.
  • 3 Drug Discovery Center, State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 51055, China.
  • 4 Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Pathophysiology, Shenzhen University Health Science Center, Shenzhen, 518060, China. liuj@szu.edu.cn.
  • 5 Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University Health Science Center, Shenzhen, 518060, China. liuj@szu.edu.cn.
  • # Contributed equally.
PMID: 33893593 DOI: 10.1007/s00395-021-00867-7
Abstract

Appropriately 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.

Keywords

C/EBP-homologous protein; Cardiac fibroblast; Hypoxia-induced mitogenic factor; Macrophage polarization; Myocardial infarction; Tissue repair.

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