Sepsis-induced cardiomyopathy (SICM) is a frequent and clinically important complication of sepsis, characterized by acute and often reversible myocardial dysfunction and associated with poor outcomes in critically ill patients. Despite growing recognition of its clinical significance, effective mechanism-based therapies remain unavailable, largely because SICM is highly heterogeneous and driven by a complex interplay of inflammatory activation, endothelial and microcirculatory dysfunction, oxidative stress, mitochondrial injury, calcium-handling abnormalities, metabolic reprogramming, and dynamic cardiomyocyte adaptation. In recent years, increasing attention has been directed toward epigenetic regulation, as it provides a mechanistic framework linking septic stress to sustained transcriptional and post-transcriptional remodeling in the myocardium and its immune microenvironment. Numerous studies have therefore investigated epigenetic mechanisms in SICM, including DNA methylation, histone modifications, and non-coding RNA-mediated regulation. This review summarizes recent advances in the understanding of epigenetic mechanisms underlying SICM, with emphasis on their roles in inflammation, mitochondrial dysfunction, immune–cardiac crosstalk, and cardiomyocyte injury. We further discuss the translational relevance of epigenetic remodeling and highlight the emerging therapeutic potential of epigenetically targeted interventions. Collectively, these findings provide important mechanistic insights into SICM and may support the development of biomarker-guided stratification and more precise therapeutic strategies for septic myocardial dysfunction.
Chen Jiang, Zhan-Fei Li, Xi-Jie Dong et al.· International Journal of Mol...· 0 citations
Abstract Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response, is characterized by a dynamic progression from hyperinflammation to immunosuppression. Its persistently high mortality underscores the limitations of therapies focused solely on immune homeostasis. This review advocates a paradigm shift that positions the nervous system as a central orchestrator of host defense through a hierarchical neuroimmune axis. This axis comprises three interconnected tiers: (1) peripheral effector pathways—the cholinergic anti-inflammatory pathway and the sympathetic-adrenal-medullary axis; (2) central integrative hubs in the brainstem (eg, nucleus tractus solitarius) and limbic system; and (3) molecular translators that convert neural signals into cellular immune responses. In sepsis, maladaptive plasticity within these circuits leads to a pathological “uncoupling” of immune sensing from neural control, driving organ dysfunction and perpetuating both runaway inflammation and subsequent immunosuppression. We critically evaluate emerging neuromodulation strategies—including bioelectronic vagus nerve stimulation, splenic focused ultrasound, precise electroacupuncture, and receptor-specific pharmacology—with careful distinction between established mechanistic evidence, preclinical findings, and early-stage clinical data. The future direction lies in precision neuromodulation, an evolving concept encompassing closed-loop systems responsive to dynamic biomarkers, chronotherapy, and targeted nanomedicine, though these approaches require substantial technical and clinical validation. This framework charts a roadmap for evolving sepsis management from supportive care toward proactive modulation of endogenous regulatory networks, while emphasizing that further mechanistic studies, biomarker validation, and well-designed clinical trials are essential prerequisites for clinical translation.
Chuntao Wang, Xiaojiang Huang, Chaoyao Hou et al.· Journal of Inflammation Rese...· 0 citations
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