MicroRNAs in dilated cardiomyopathy: from biomarkers to therapeutic targets

Dilated cardiomyopathy (DCM) remains a leading cause of non-ischemic heart failure and sudden cardiac death, with substantial heterogeneity in clinical presentation and outcomes. Conventional diagnostic tools and circulating protein biomarkers largely reflect late-stage myocardial injury and fail to capture the underlying molecular complexity of the disease. MicroRNAs (miRNAs), small non-coding RNAs that regulate post-transcriptional gene expression, have emerged as promising biomarkers and therapeutic targets in cardiovascular disorders. Dysregulated microRNAs signatures are closely linked to key pathological processes including myocardial fibrosis, inflammation, apoptosis, angiogenesis impairment, and metabolic remodeling. Circulating miRNAs demonstrate remarkable stability in biofluids and show potential for early detection, risk stratification, and monitoring of disease progression. This review focuses on the current evidence on the role of circulating and tissue-derived miRNAs in the pathogenesis, diagnosis, and treatment of dilated cardiomyopathy. It further discusses emerging therapeutic strategies based on miRNA modulation, including the use of miRNA mimics and anti-miRs, which have shown promising preclinical and early clinical outcomes. However, significant translational challenges, including delivery specificity, off-target effects, molecular instability, and lack of methodological standardization, continue to limit the clinical implementation of miRNA-based therapies in DCM.