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Background <p>Sepsis-induced cardiomyopathy (SICM) is a critical cardiovascular complication characterized by cardiac dysfunction and high mortality. The molecular mechanisms that underlie SICM remain elusive, and effective therapies are limited.</p> Results <p>Here, we report a pivotal role for adenosine deaminases acting on RNA-1 (ADAR1) in modulating macrophage polarization and exosome-mediated intercellular communication, which ameliorates myocardial damage in SICM. We determined that ADAR1 overexpression in macrophages promotes an anti-inflammatory M2 phenotype, reduces myocardial inflammation, and inhibits cardiomyocyte apoptosis in a murine model of sepsis. Mechanistically, ADAR1 regulates the level of microRNA-122 (miR-122) in macrophage-derived exosomes. Exosomal miR-122 targets X-linked inhibitor of apoptosis protein (XIAP), modulating cardiomyocyte survival.</p> Conclusions <p>Our study reveals a novel ADAR1-miR-122-XIAP axis in macrophage exosomes that protects against sepsis-induced myocardial injury, offering a potential disease modulation strategy for SICM.</p> Graphical abstract <p></p>

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Therapeutic potential of ADAR1-regulated macrophage exosomes for improving myocardial damage in septic cardiomyopathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月11日

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  • Linxiao Wang,
  • Shanshou Liu,
  • Xianqi Wang,
  • Huirong Wu,
  • Xiaojun Zhao,
  • Dan Wu,
  • Qianmei Wang,
  • Peiwen Wang,
  • Yanan Xu,
  • Kuo Shen,
  • Juzheng Yuan,
  • Junjie Li

摘要

Background

Sepsis-induced cardiomyopathy (SICM) is a critical cardiovascular complication characterized by cardiac dysfunction and high mortality. The molecular mechanisms that underlie SICM remain elusive, and effective therapies are limited.

Results

Here, we report a pivotal role for adenosine deaminases acting on RNA-1 (ADAR1) in modulating macrophage polarization and exosome-mediated intercellular communication, which ameliorates myocardial damage in SICM. We determined that ADAR1 overexpression in macrophages promotes an anti-inflammatory M2 phenotype, reduces myocardial inflammation, and inhibits cardiomyocyte apoptosis in a murine model of sepsis. Mechanistically, ADAR1 regulates the level of microRNA-122 (miR-122) in macrophage-derived exosomes. Exosomal miR-122 targets X-linked inhibitor of apoptosis protein (XIAP), modulating cardiomyocyte survival.

Conclusions

Our study reveals a novel ADAR1-miR-122-XIAP axis in macrophage exosomes that protects against sepsis-induced myocardial injury, offering a potential disease modulation strategy for SICM.

Graphical abstract