Rewriting the Cardiovascular Transcriptome: Emerging Roles of PIWIInteracting RNAs as Epigenetic Modulators and...

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs originally identified in germ cells, are now increasingly recognized as pivotal regulators of gene expression in somatic tissues, including the cardiovascular system. Cardiovascular diseases (CVDs) remain the leading global cause of morbidity and mortality, yet sensitive and specific molecular biomarkers and effective RNA-based therapeutic targets are still lacking. However, compared to microRNAs and lncRNAs, the roles of piRNAs in CVD are only beginning to be elucidated, highlighting an important knowledge gap. The objective of this review was to synthesize current evidence on piRNA functions in cardiovascular biology, with emphasis on disease-specific mechanisms and translational implications. To achieve this, we conducted a literature search in PubMed and Web of Science databases (2015-2025) using the keywords "piRNA" OR "PIWIinteracting RNA" combined with "cardiovascular", "heart failure", "ischemia reperfusion", "myocardial infarction", "aortic valve", and "pulmonary hypertension". This review has not only summarized existing findings, but also highlighted emerging opportunities and challenges for advancing piRNA-based diagnostics and therapeutics in cardiovascular medicine.