Circulating exRNA Signatures Predicting Adverse Cardiac Remodeling Post-MI

Background: Adverse cardiac remodeling following myocardial infarction (MI) is a key determinant of progression to heart failure, characterized by chamber dilation, fibrosis, wall thinning, and contractile dysfunction. Early identification of patients at high risk for maladaptive remodeling remains an unmet clinical need. Circulating extracellular RNAs (exRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, have emerged as promising non-invasive biomarkers with diagnostic and prognostic potential. These exRNAs are packaged in exosomes or bound to protein complexes, reflecting dynamic cellular responses to myocardial injury. Methods and Results: In this multicenter prospective study, plasma samples were collected from patients with acute MI at admission, 24 hours, 7 days, and 6 months. High-throughput small RNA sequencing and bioinformatic deconvolution identified a panel of differentially expressed exRNAs strongly associated with left ventricular ejection fraction decline, scar size, and fibrosis markers on cardiac MRI at 6-month follow-up. Notably, upregulation of miR-21-5p, miR-199a-3p, and lncRNA LIPCAR, along with downregulation of miR-30d and miR-29c, consistently predicted adverse remodeling outcomes independent of clinical variables. Pathway enrichment analysis revealed targeting of TGF-β, Wnt, and apoptosis signaling cascades. Validation in an independent cohort and functional studies in cardiomyocytes and fibroblasts confirmed causal roles in hypertrophy, collagen deposition, and myofibroblast activation. Conclusion: Circulating exRNA signatures offer a powerful, minimally invasive tool for early risk stratification of post-MI patients prone to adverse cardiac remodeling. These molecular fingerprints not only hold clinical utility as biomarkers but also reveal novel mechanistic pathways involved in remodeling, laying the foundation for exRNA-guided precision medicine approaches in post-infarction care.