REVIEW article
Front. Immunol.
Sec. Inflammation
The Immunometabolic Axis of Sepsis-Related Myocardial Injury: Macrophage Reprogramming as a Central Mechanism and Therapeutic Target
Yuyang Qiu 1,2
Hongying Bi 2
Xie Wei 1
Jiao Zhao 1
Tian Zhang 1
Jianyu Fu 2
Xu Liu 2
Guiyun Li 1
1. The Second People's Hospital of Guiyang (Jinyang Hospital) / The Affiliated Jinyang Hospital of Guizhou Medical University, guiyang, China
2. The Affiliated Hospital of Guizhou Medical University, Guiyang, China
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Abstract
Sepsis-related myocardial injury (SRMI) is a major cause of death in critically ill patients, with pathogenesis extending beyond inflammation to encompass dysregulated immunometabolic crosstalk. This review elucidates macrophage metabolic reprogramming as a central mechanism driving SRMI, detailing how a shift to aerobic glycolysis fuels pro-inflammatory responses, while oxidative phosphorylation supports reparative functions. We emphasize that metabolites like succinate, itaconate, and lactate act as potent signaling molecules, orchestrating epigenetic changes and inflammatory pathways. Furthermore, we deconstruct the critical immunometabolic dialogue mediated by extracellular vesicles (EVs) and signaling cascades among macrophages, cardiomyocytes, and endothelial cells. Translating these insights, we evaluate next-generation therapeutic strategies aimed at this immunometabolic axis, including precision small-molecule modulators, nucleic acid-based technologies, and biologics. These approaches represent a promising strategic shift from non-specific immunosuppression toward targeted immunometabolic modulation. This synthesis provides a foundational framework for understanding SRMI and charts a roadmap for developing novel precision medicine interventions to improve patient outcomes.
Summary
Keywords
Exosomes, Immunometabolism, macrophagepolarization, metabolic reprogramming, Mitochondria, Sepsis-relatedmyocardialinjury
Received
02 January 2026
Accepted
20 February 2026
Copyright
© 2026 Qiu, Bi, Wei, Zhao, Zhang, Fu, Liu and Li. 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: Yuyang Qiu; Xu Liu; Guiyun Li
Disclaimer
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