# Mechanisms and therapeutic strategies of copper homeostasis in the pathogenesis of sepsis-induced cardiomyopathy

## TL;DR

This paper reviews how copper imbalance contributes to heart damage in sepsis and explores potential treatments targeting copper homeostasis.

## Contribution

The paper provides a comprehensive overview of copper-related mechanisms in sepsis-induced cardiomyopathy and novel therapeutic strategies.

## Key findings

- Copper imbalance disrupts heart cell function through lipid metabolism and endoplasmic reticulum stress.
- Copper-related cell death forms like cuproptosis and apoptosis are linked to sepsis-induced cardiomyopathy.
- Potential therapies include copper chelators, transport inhibitors, and natural products targeting copper homeostasis.

## 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.