Metrnl ameliorates myocardial ischemia–reperfusion injury by activating AMPK-mediated M2 macrophage polarization

作者：Dexin Chen, Yang-Yi Feng, Haiyan Wang, Chuanghong Lu, De-Zhao Liu, Gong� Chen, Yan Xue, Na Na, Feng Huang · 发表于：Molecular Medicine · 年份：2025 · DOI：10.1186/s10020-025-01150-4 · 被引用次数：22 · 研究领域：Adipose Tissue and Metabolism、Immune cells in cancer、Adipokines, Inflammation, and Metabolic Diseases

BACKGROUND: Meteorin-like hormone (Metrnl) is prominently expressed in activated M2 macrophages and has demonstrated potential therapeutic effects in a range of cardiovascular diseases by modulating inflammatory responses. Nevertheless, its precise role and the underlying mechanisms in myocardial ischemia/reperfusion injury (MI/RI) are not fully understood. This study examined whether Metrnl can mitigate MI/RI through the AMPK-mediated polarization of M2 macrophages. METHODS: In vivo, adeno-associated virus 9 containing the F4/80 promoter (AAV9-F4/80) was utilized to overexpress Metrnl in mouse cardiac macrophages before MI/RI surgery. In vitro, mouse bone marrow-derived macrophages (BMDMs) were treated with recombinant protein Metrnl, and the human cardiomyocyte cell line AC16 was subjected to hypoxia/reoxygenation (H/R) after co-culture with the supernatant of these macrophages. Cardiac function was assessed via echocardiography, H&E staining, and Evans blue-TTC staining. Inflammatory infiltration was evaluated by RT-qPCR and ELISA, apoptosis by Western blotting and TUNEL staining, and macrophage polarization by immunofluorescence staining and flow cytometry. RESULTS: In vivo, Metrnl overexpression in cardiac macrophages significantly attenuated MI/RI, as evidenced by reduced myocardial infarct size, enhancement of cardiac function, diminished inflammatory cell infiltration, and decreased cardiomyocyte apoptosis. Furthermore, Metrnl overexpression promoted M1 to M2 macropha...