Regulatory roles of PIWI-interacting RNAs in cardiovascular disease

Cardiovascular disease remains the number one cause of death worldwide. Across the spectrum of cardiovascular pathologies, all are accompanied by changes in gene expression profiles spanning a variety of cellular components of the myocardium. Alterations in gene expression are regulated by small noncoding RNAs (sncRNAs), with P-element-induced WImpy testis (PIWI)-interacting RNAs (piRNAs) being the most abundant of the sncRNAs in the human genome. Composed of 21-35 nucleotides in length with a protective methyl group at the 3' end, piRNAs complex with highly conserved RNA-binding proteins termed PIWI proteins to recruit enzymes used for histone, DNA, RNA, and protein modifications. Thus, specific piRNA expression patterns can be exploited for early clinical diagnosis of cardiovascular disease and the development of novel RNA therapeutics that may improve cardiac health outcomes. This review summarizes the latest progress made on understanding how piRNAs regulate cardiovascular health and disease progression, including a discussion of their potential in the development of biomarkers and therapeutics.