Atheroprotective roles of exercise-regulated microRNAs

Cardiovascular disease remains the leading cause of death worldwide, with atherosclerosis (AS) serving as a critical underlying pathological process and major risk factor. Regular physical exercise is widely recognized as an effective strategy to reduce the risks and severity of AS, yet the precise molecular mechanisms through which exercise exerts its protective effects are still not fully understood. MicroRNAs (miRNAs), key regulators of gene expression, play integral roles in the progression of AS by influencing vascular function, lipid metabolism, and inflammation. The exercise-induced improvement of AS is a complex process, with miRNAs playing essential roles not only within cells and tissues but also circulating stably in the bloodstream as novel signaling molecules. These circulating miRNAs mediate communication between organs and tissues, acting as potential biomarkers that could provide deeper, systemic insights into the metabolic benefits of exercise. In this review, we explore recent advancements in our understanding of how exercise affects both intracellular and circulating miRNAs. We emphasize how exercise-regulated miRNAs contribute to endothelial function, promote lipid metabolism across various metabolic organs, and reduce monocyte-mediated systemic inflammation, while also addressing their role in alleviating frailty. Circulating miRNAs, which dynamically reflect tissue-specific responses to exercise, hold great promise as diagnostic and prognostic biomarkers for AS. Moreover, we discuss the challenges and future directions in this field, aiming to uncover how exercise-induced miRNA modulation could offer innovative therapeutic strategies for the prevention and treatment of AS.