Systemic microRNA profiles associated with coronary plaque stability and clinical phenotypes in patients with coronary artery disease

Background The development of coronary artery disease (CAD) and plaque destabilization are caused by endothelial dysfunction, inflammation and hypoxia. Recent studies suggest that circulating microRNAs (miRNAs) constitute promising non‐invasive biomarkers for monitoring these pathophysiological mechanisms. Methods In this exploratory study, we profiled circulating miRNAs in patients with stable versus unstable CAD and investigated the associations with plaque instability, comorbidities and sex‐specific modulation. Results Different expression patterns were observed. miR‐320‐3p was nominally reduced in unstable CAD, consistent with its role in endothelial integrity and blood coagulation, but this reduction was not statistically significant after correction. Sex‐specific increases in miR‐21 isoforms and miR‐210 were observed in women with unstable CAD, suggesting hormonal and inflammatory influences. Different associations of miR‐103a‐5p and miR‐146b‐5p with metabolic stress, as well as an accumulation of inflammatory, metabolic and hypoxia‐responsive miRNAs, underscore the presence of coordinated regulatory networks. Conclusions This pilot study identified circulating miRNA signatures associated with plaque instability and sex‐dependent vascular modulation. Although these results are preliminary, they provide a mechanistic and translational framework for integrating circulating miRNAs into multimodal risk stratification, thus complementing imaging techniques and conventional biomarkers. Larger longitudinal studies are needed to confirm predictive value and clinical utility.