Home General Physiology and Biophysics 2025 General Physiology and Biophysics Vol.44, No.5, p. 377–389, 2025

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Founded: 1982
ISSN 1338-4325 (online)
ISSN 0231-5882 (print)
Published in English,
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General Physiology and Biophysics Vol.44, No.5, p. 377–389, 2025

Title: Hypoxia-conditioned cardiomyocyte-derived exosomes attenuate myocardial injury via ANP-mediated M2 macrophage polarization
Author: Mingye Wang, Chi Zhao, Tongtong Li, Tao Song, Yuanyuan Hao, Wenwen Cui, Min Guan, Yunlong Hou, Yang Li
Abstract: Exosomes derived from various cells have been demonstrated to contribute to cardiac repair by regulating macrophage polarization in myocardial infarction. However, how exosomes secreted from cardiomyocytes under hypoxia-ischemia (Hypo-Exo) regulate macrophage polarization in the local tissues is elusive. This study aimed to determine the underlying mechanisms by which Hypo-Exo polarized M2 macrophages. Hypo-Exo was harvested from the supernatant of oxygen glucose deprivation (OGD)-conditioned H9c2, identified using transmission electron microscopy, nanoparticle tracking analysis, and Western blot, and then applied to RAW264.7 and C57BL/6N mice. Echocardiography, TTC, H&E, Masson, and immunofluorescence staining were used to evaluate the therapeutic effects of Hypo-Exo in the myocardial infarction injury (MI) mouse model. The effects of Hypo-Exo on RAW264.7 were examined by RT-qPCR. Hypo-Exo labeled with PKH26 could be engulfed by RAW264.7 cells and promote M2 macrophage polarization. Hypo-Exo inhibited atrial natriuretic peptide (ANP) mRNA expression in RAW264.7 cells, and three cargo miRNAs of Hypo-Exo were upregulated to degrade the ANP expression. Instead of downregulating ANP, OGD supernatant upregulated ANP expression to activate M1 macrophages. Our study demonstrated a novel mechanism that Hypo-Exo carried with miRNAs as a communicator to degrade the expression level of ANP mRNA in macrophages by which Hypo-Exo polarized M2 macrophages to improve recovery from MI in mice.
Keywords: Hypo-Exo — Macrophages — ANP — Myocardial infarction — Inflammatory
Year: 2025, Volume: 44, Issue: 5 Page From: 377, Page To: 389
doi:10.4149/gpb_2025022


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