The Hidden Regulators: MicroRNAs in Pediatric Heart Development and Disease.

The development and function of the heart are governed by a highly coordinated network of regulatory mechanisms, among which miRNAs play a central role. These small, non-coding molecules modulate gene expression predominantly through mRNA degradation. This narrative review aims to summarize current knowledge about biogenesis, its impact on heart development and function, and its clinical implications in pediatric cardiology. We discuss how specific miRNAs contribute to shaping the normal heart and influencing the pathogenesis of congenital malformations. Furthermore, we review disease-specific miRNA signatures identified in the most common congenital heart defects and some acquired diseases, including hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), bicuspid aortic valve (BAV), septation defects, cardiomyopathies, arrhythmias, and myocarditis. Many studies indicate that circulating and tissue miRNAs can become non-invasive biomarkers for early diagnosis and disease monitoring. Experimental data suggest their potential use in treatment despite many delivery and safety challenges. However, further research is necessary to fully exploit the potential of miRNAs and effectively translate these findings into clinical practice in pediatric cardiology.