MicroRNA-21 and MicroRNA-208a as Biomarkers of Myocardial Remodeling Post-Infarction

Background Myocardial remodeling following acute myocardial infarction (AMI) is a critical determinant of long-term cardiac function and progression to heart failure. Conventional biomarkers provide limited insight into the molecular mechanisms underlying this process. MicroRNAs (miRNAs), particularly microRNA-21 (miR-21) and microRNA-208a (miR-208a), have emerged as potential regulators of fibrosis and myocardial injury, respectively, and may serve as novel biomarkers of post-infarction remodeling. Objective To evaluate the clinical utility of circulating miR-21 and miR-208a as biomarkers for predicting myocardial remodeling in patients following acute myocardial infarction. Methods This prospective observational study was conducted at two tertiary centers in Italy and included 60 patients with confirmed AMI and 20 healthy controls. Plasma levels of miR-21 and miR-208a were measured using quantitative real-time PCR at admission (T0), 72 hours (T1), and 3 months (T2). Echocardiographic assessment of left ventricular function and volumes was performed at baseline and 3-month follow-up. Adverse remodeling was defined as a ≥20% increase in left ventricular end-diastolic volume. Statistical analysis included correlation studies, receiver operating characteristic (ROC) curve analysis, and multivariate logistic regression. Results Both miR-21 and miR-208a levels were significantly elevated in AMI patients compared to controls (p < 0.001). MiR-21 peaked at 72 hours (5.2 ± 1.6-fold increase), while miR-208a showed highest levels at admission (4.5 ± 1.5-fold). Adverse remodeling occurred in 36.7% of patients. MiR-21 levels were significantly higher in patients with remodeling (5.9 ± 1.4 vs 3.7 ± 1.1; p < 0.001) and showed strong correlations with left ventricular ejection fraction (r = −0.62) and LVEDV (r = 0.58). MiR-208a correlated with troponin levels (r = 0.65, p < 0.001) and remodeling status (p = 0.002). ROC analysis demonstrated good predictive performance for miR-21 (AUC = 0.87) and miR-208a (AUC = 0.82), with improved accuracy when combined (AUC = 0.91). Multivariate analysis identified miR-21 and miR-208a as independent predictors of remodeling. Conclusions Circulating miR-21 and miR-208a are promising non-invasive biomarkers for assessing myocardial remodeling following AMI. MiR-21 is strongly associated with fibrotic remodeling, whereas miR-208a reflects myocardial injury severity. Their combined use enhances predictive accuracy and may support early risk stratification and personalized management of patients with post-infarction conditions. Keywords: MicroRNA-21; MicroRNA-208a; Myocardial Infarction; Cardiac Remodeling; Biomarkers; Left Ventricular Dysfunction; Fibrosis