The potential of TRPC channel-mediated autophagy in myocardial ischemia-reperfusion injury.

BACKGROUND

Myocardial ischemia/reperfusion injury (MI/RI) is a common complication in the treatment of acute myocardial infarction, which is often accompanied by high disability rate and mortality.Autophagy is a highly conserved cellular process widely observed in eukaryotic cells, serving as a critical mechanism for the removal of damaged, dysfunctional, or aged intracellular components. As a vital self-protective pathway, autophagy plays an essential role in maintaining cellular homeostasis. Accumulating evidence indicates that autophagy is implicated in calcium overload during MI/RI. The transient receptor potential canonical (TRPC) channels, which function as Ca²⁺-permeable non-selective cation channels, are known to participate in various Ca²⁺-related pathological processes.

METHODS

A comprehensive literature review was conducted using established scientific databases, including ScienceDirect, PubMed, and Google Scholar. This article focuses on the pathogenesis of MI/RI, the TRPC channel family, and their interrelationships. Relevant research findings were systematically summarized, and potential directions for future investigation were discussed.

MAIN BODY: This review examines the key pathophysiological mechanisms underlying myocardial ischemia-reperfusion injury, including inflammatory responses, calcium overload, and oxidative stress. Particular emphasis is placed on calcium overload, with a detailed exploration of its molecular mechanisms. Furthermore, autophagy and the associated signaling pathways-specifically the CaMKKβ/AMPK/mTOR axis-are discussed to elucidate the interplay between autophagy and calcium regulation, as well as the protective effects of autophagy in the context of MI/RI. Additionally, the structure, function, and current research progress on the TRPC channel family in relation to MI/RI are reviewed, providing insights into potential future research avenues.

CONCLUSION

Currently, the effective treatment of myocardial ischemia-reperfusion injury remains a significant clinical challenge. Evidence suggests that downregulation of TRPC channel expression may mitigate Ca²⁺ overload and thereby reduce cellular damage. However, whether this protective effect is mediated through autophagy requires further experimental validation and mechanistic investigation.