Circulating exosomal miRNA in acute coronary syndrome: mechanisms, clinical relevance and future directions.

Despite significant advances in diagnosis and treatment, Acute Coronary Syndrome (ACS) remains one of the leading causes of morbidity and mortality globally. It comprises ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and unstable angina, caused by complex mechanisms such as plaque rupture, thrombosis, erosion, and microvascular dysfunction. The development of high-sensitivity cardiac troponins has greatly improved the early detection of ACS. However, concerns remain about specificity, timing, and prognostic accuracy. Exosomal miRNAs (ExomiRs) show promise as minimally invasive biomarkers, aiding precise cell communication and protecting encapsulated miRNAs from degradation. During ischemic injury, ExomiRs released from cardiomyocytes act early, often before troponin elevation, and are involved in processes such as inflammation, apoptosis, angiogenesis, fibrosis, and ventricular remodelling. Specific ExomiR signatures have different roles in prognosis, subtype discrimination, and early ACS diagnosis. Future therapeutic potential may include advancements in translational strategies, such as antagomir-based miRNA modulation. Furthermore, the clinical adoption of these biomarkers, despite challenges such as pre-analytical variability, differences across study cohorts, a lack of standardised isolation protocols, and the need for large-scale validation, will significantly improve the sensitivity, specificity, and accuracy of predicting ACS.