REVIEW article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Mechanisms and therapeutic strategies of copper homeostasis in the pathogenesis of Sepsis-induced cardiomyopathy
Provisionally accepted
- 1Hunan Normal University School of Medicine, Changsha, China
- 2Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, changsha, China
- 3People’s Hospital of Honghu City, Honghu, China
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ABSTRACT Sepsis-induced cardiomyopathy (SCM) is a severe, mortality-increasing sepsis complication, with copper homeostasis imbalance as a key pathogenic factor. Copper (Cu) plays a dual role: as an essential enzyme cofactor, it regulates vital processes including energy metabolism and redox balance; however, both excess and deficiency disrupt cellular homeostasis and induce cardiomyocyte injury. This review summarizes core pathophysiological mechanisms linking copper homeostasis imbalance to SCM, including abnormal copper metabolism (dysregulated uptake/transport/excretion), lipid metabolism disorders, endoplasmic reticulum stress (ERS), and various regulated cell death (RCD) forms (cuproptosis, apoptosis, autophagy, pyroptosis, ferroptosis, necrosis). We also elaborate potential therapeutic strategies targeting copper homeostasis, including copper chelators, copper transport inhibitors, copper-mediated RCD modulators, multi-target natural products, nanopreparations, and latest advances in copper-based myocardial injury therapy. Finally, we address current research limitations and outline future directions, such as exploring copper-related cell death markers, clarifying underexplored copper signaling in SCM, and developing innovative precision therapies. This review offers a comprehensive theoretical foundation for further investigating copper homeostasis in SCM and developing novel therapies.
Keywords: Cell Death, copper homeostasis, cuproptosis, Sepsis, Sepsis-induced cardiomyopathy
Received: 24 Nov 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Xie, Wang, You, Li, Li and Wu. 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: Huaying Wu
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