ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1629676
Large Extracellular Vesicles Derived from LPS-preconditioned Cardiomyocytes Alleviate Myocarditis via Mediating Macrophage Polarization and Modulating p38 MAPK Pathway
Provisionally accepted
- 1Shandong University, Jinan, China
- 2Shandong Provincial Hospital, Jinan, China
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Myocarditis is an inflammatory injury to the myocardium characterized by disrupted intercellular communication, involving macrophages and cardiomyocytes as key players. However, the interactions between macrophages and cardiomyocytes during myocarditis remain inadequately explored. Emerging evidence indicated that extracellular vesicles (EVs) play a crucial role in intercellular communication. Here, we demonstrated that large EVs derived from lipopolysaccharide (LPS)-preconditioned cardiomyocytes (C-lEVLPS) exhibited anti-inflammatory effects on macrophages and alleviated cardiac inflammation and dysfunction in a mouse model of CVB3-induced myocarditis. Additionally, C-lEVLPS facilitated macrophage polarization toward the M2-like phenotype and inhibits M1 polarization, both in vitro and in vivo. Notably, compared to phosphate-buffered saline (PBS)-preconditioned cardiomyocytes (C-lEVPBS), C-lEVLPS was enriched in the phosphatase 2 scaffold subunit alpha protein (PP2AA), which can recruit other subunits to form the PP2A complex, ultimately leading to the dephosphorylates of p38. This study highlights the effect of C-lEVLPS in myocarditis and uncovers the potential mechanism that modulates macrophage polarization by delivering PP2AA from cardiomyocytes to macrophages and regulating the p38 MAPK pathway. These findings provide a promising therapeutic strategy for myocarditis.
Keywords: Myocarditis, cardiomyocytes, Macrophages, large extracellular vesicles, MAPK
Received: 16 May 2025; Accepted: 14 Aug 2025.
Copyright: © 2025 Jiang, You, Xie, Zhou, Ma and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bo Han, Shandong Provincial Hospital, Jinan, China
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