REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1643048
This article is part of the Research TopicImmunomodulatory Strategies in Perioperative Organ Protection: From Mitochondrial Dysfunction to Clinical ApplicationsView all 3 articles
Combatting Sepsis-Induced Myocardial Dysfunction: Emerging Mechanisms and Immunomodulatory Breakthroughs
Provisionally accepted
- Southwest Medical University, Luzhou, China
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Sepsis-induced myocardial dysfunction (SIMD) critically contributes to mortality in systemic inflammatory responses, driven by multifaceted mechanisms including dysregulated inflammation, immunosuppression, oxidative stress, and autonomic dysfunction. Emerging pathways involve m6A RNA methylation (mediated by methyltransferase METTL3), which coordinates inflammation, apoptosis, and ferroptosis through transcriptomic rewiring. Extracellular vesicles (EVs) serve dual roles: propagating injury via microRNA-885-5p/HMBOX1-induced pyroptosis and delivering therapeutic cargo (e.g., microRNA-223) to suppress inflammation. Mitochondrial dysfunction, marked by reactive oxygen species (ROS)-NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and impaired sarco/endoplasmic reticulum calcium ATPase 2a (SERCA2a) stability, exacerbates metabolic disorder. Autonomic neuromodulation strategies, such as electroacupuncture and noninvasive vagus nerve stimulation, attenuate cardiac injury by rebalancing neuroimmune interactions. Complement hyperactivation (C5a-C5a receptor axis) and immune checkpoint inhibitors (e.g., anti-programmed death-ligand 1 [PD-L1] antibodies) show preclinical efficacy. However, challenges persist in addressing immune heterogeneity, dynamic biomarker profiling, and optimal therapeutic timing. This review bridges mechanistic discoveries to clinical innovation, proposing a paradigm shift toward precision therapies. Future research must bridge mechanistic insights with clinical innovation. By harmonizing pathophysiological understanding with precision medicine approaches, this synthesis underscores the potential to transform SIMD management from supportive care to targeted functional recovery.
Keywords: Sepsis, Myocardial injury, Inflammation, Sepsis-induced myocardial dysfunction, targeted therapy
Received: 20 Jun 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Liu, Liu, Li, Zeng, Wang, Mou, Liao and Wan. 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: Bin Liao, liaobin@swmu.edu.cn
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