Role of Exosomal miRNAs in Cardiovascular Disease: Potential Biomarkers and Therapeutic Targets

Abstract

Background: Exosomal microRNAs (miRNAs) mediate intercellular signaling and have emerged as potential biomarkers in cardiovascular disease (CVD), offering diagnostic and therapeutic relevance beyond conventional biochemical markers. Objective: This study aims to investigate the diagnostic utility of exosomal miRNAs in CVD, focusing on their expression variability, predictive accuracy, and therapeutic implications within a Bangladeshi multicenter tertiary cohort. Methods: A prospective observational study was conducted across three tertiary hospitals in Bangladesh from January 2023 to December 2024. A total of 114 patients with confirmed CVD diagnoses were enrolled. Plasma exosomes were isolated using ultracentrifugation, quantified by nanoparticle tracking analysis, and miRNA profiles were assessed through quantitative RT-PCR. Expression levels of selected miRNAs (miR-21, miR-126, miR-133a, miR-208a, and miR-499) were normalized against U6 controls. Statistical analysis included ANOVA, ROC curve analysis, Pearson correlation, and logistic regression to determine diagnostic sensitivity, specificity, and therapeutic predictive potential. Results: Exosomal miR-21 and miR-126 levels were significantly elevated in CVD patients compared with healthy controls (p<0.001). Mean fold increase of miR-21 was 3.42 ± 0.87 (95% CI: 2.91–3.93), while miR-126 increased by 2.78 ± 0.65 (95% CI: 2.49–3.07). ROC analysis demonstrated high diagnostic accuracy: miR-21 (AUC=0.91, sensitivity 88.6%, specificity 84.2%), miR-126 (AUC=0.88, sensitivity 85.3%, specificity 82.1%). Logistic regression indicated combined miR-21/miR-126 expression predicted adverse remodeling with OR=3.54 (p=0.002). Standard deviation in inter-patient variability was 0.87 for miR-21 and 0.65 for miR-126, confirming statistical robustness. Conclusion: Exosomal miR-21 and miR-126 are reliable biomarkers with strong diagnostic and prognostic potential in CVD, highlighting their applicability as non-invasive therapeutic targets in Bangladesh.