Skeletal Muscle sEVs Mediate Exercise-Induced Cardioprotection in I/R Injury.

Exercise in mice increases skeletal muscle-derived small extracellular vesicle entry into the heart, and these sEVs significantly attenuate myocardial ischemia/reperfusion injury.

• Why it matters: The mechanism linking exercise training to endogenous cardioprotection is unclear, particularly how skeletal muscle communicates with the heart during ischemia/reperfusion.
• What they did: Mice were tracked using an adeno-associated virus 8-dMCK-CD63-EGFP reporter after 4 weeks of exercise; sEV secretion was manipulated via intramyocardial sEV injection or skeletal muscle-specific Rab27a knockout, and sEV microRNAs were profiled and tested in cardiomyocytes and MI/R models.
• The result: Exercise-enriched sEVs delivered miR-451a and miR-143-3p, modulating PERK-ATF4-CHOP and USP46/P53 to reduce cardiomyocyte death; miRNA overexpression recapitulated protection, and human exercise cohorts showed elevated miR-451a/143-3p in skeletal muscle and circulating sEVs.

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