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

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.

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.

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.

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.