Exercise-induced muscle exosomes: microRNA cargo as regulators of cardiovascular remodeling and disease progression

Cardiovascular diseases (CVD) are a primary cause of global morbidity and mortality, with incomplete understanding of how lifestyle factors like exercise provide protection. Skeletal muscle functions as a secretory organ, releasing exosomes containing microRNAs (miRNAs) that facilitate intercellular communication and influence inflammation, angiogenesis, and cardiac remodeling. This review synthesizes recent literature on exercise-induced, muscle-derived exosomal miRNAs in cardiovascular biology. It emphasizes key miRNAs (miR-1, miR-133a/b, miR-206, miR-486) modulated by physical activity, their roles in endothelial function, myocardial repair, and vascular adaptation, as well as underlying cellular and molecular mechanisms and biomarker potential. Insights are integrated from molecular biology, exercise physiology, and cardiovascular research. Exercise dynamically alters exosomal miRNAs, with high-intensity interval training (HIIT) inducing a 2- to 3-fold increase in circulating exosomal miR-133a, which reduces cardiac fibrosis by targeting connective tissue growth factor (CTGF). These miRNAs mediate protective effects on endothelial function, myocardial repair, and vascular adaptation, positioning them as biomarkers of cardiovascular health. Exosomal miRNAs serve as key mediators of exercise-induced systemic adaptations and hold promise as targets for precision diagnostics and therapeutic interventions in CVD. Not applicable.