Silent controllers: non-coding RNAs drive autophagic response in myocardial ischemia reperfusion injury.

Acute myocardial infarction (AMI) continues to be a major contributor to global illness and death. Restoring coronary blood flow is a key strategy for limiting myocardial damage after infarction. Nevertheless, the re-establishment of circulation can paradoxically trigger ischemia-reperfusion (IR) injury through multiple intricate mechanisms. Consequently, IR injury remains an important obstacle in the effective management of myocardial infarction. Aberrant autophagy represents a major factor causing IR-related cardiomyocyte death. Autophagy, a catabolic process essential for cellular homeostasis, plays a bimodal role in myocardial IR -protective during ischemia yet potentially deleterious during reperfusion. Recent research highlights the pivotal regulatory function of non-coding RNAs (ncRNAs) which include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in modulating autophagy during myocardial IR injury, particularly in murine models. ncRNAs influence key autophagy regulators such as Beclin-1, ULK1, ATG5, ATG7, ATG12, LC3 and mTOR, forming complex regulatory networks that determine cardiomyocyte fate. This review synthesizes current evidence on how ncRNAs orchestrate autophagy in the setting of myocardial IR injury, elucidating underlying mechanisms and translational potentials. Understanding ncRNA-mediated modulation of autophagy opens avenues for targeted interventions to ameliorate IR injury related cardiac damage.