Remote ischemic preconditioning and exercise-induced cardioprotection via extracellular vesicle-delivered microRNAs

Ischemic heart disease remains a major global health burden, with ischemia-reperfusion injury representing a critical determinant of myocardial damage. Remote ischemic conditioning (RIC) and differentiated physical exercise regimens have emerged as potential preconditioning strategies enhancing myocardial resilience, and increasing evidence suggests that these cardioprotective effects may, in part, be mediated by targeted delivery of extracellular vesicle (EV)-carried microRNAs (miRNAs). RIC induces rapid alterations in circulating EV cargo, including miRNAs known to promote cell survival, attenuate oxidative stress, and modulate inflammation. This transient yet pronounced miRNA response to RIC indicates a rapid EV-associated molecular change that may be relevant to early signaling events underlying remote organ preconditioning. EV-miRNA content also changes acutely in response to exercise. These changes are associated with vascular remodeling, anti-apoptotic signaling, and metabolic adaptations, suggesting that exercise-induced EVs provide both immediate and sustained cardioprotection, although temporal dynamics remain incompletely defined. Consequently, RIC and exercise elicit distinct yet overlapping EV-miRNA signatures that may affect myocardial preconditioning. Here, we review whether EV-delivered miRNAs elicited by RIC and exercise may contribute to cardioprotection and may be therapeutically exploited in clinical settings such as heart failure and ischemic disease.