piRNA, the hidden player in cardiac fibrosis: A review

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs that associate with the PIWI protein family and play essential roles in germline development. Cardiac fibrosis, a terminal pathological manifestation in various cardiovascular diseases (CVDs), has garnered increasing attention for its molecular regulatory mechanisms. Emerging studies have shown that piRNAs can participate in key pathological processes-such as the activation of cardiac fibroblasts (CF) and extracellular matrix (ECM) remodeling-through mechanisms such as epigenetic regulation and targeted mRNA degradation. This review systematically summarizes the biogenesis of piRNAs, their expression patterns in cardiac fibrosis, and their underlying mechanisms of action. It also discusses how piRNAs may influence CVDs by modulating fibroblast function and explores the potential of piRNAs as novel biomarkers and therapeutic targets. These insights provide a theoretical basis for a deeper understanding of the pathogenesis of cardiac fibrosis and the development of innovative intervention strategies.