Extracellular vesicle YRNA in atherosclerosis.

Atherosclerosis is characterized by lipid accumulation and chronic inflammation. The accumulation of apoptotic foam cells can induce the secretion of proinflammatory factors and necrosis of atherosclerotic plaque tissue. Numerous studies have demonstrated that extracellular vesicle (EV)-enclosed YRNAs and their fragments, YsRNAs, play important roles in atherosclerosis initiation, progression, and diagnosis. YsRNA-5p transcripts promote foam cell apoptosis and inflammatory responses by binding to Ro60 in vitro and in vivo. YRNAs may regulate atherosclerosis progression by binding to several proteins, including nucleolin, Ro60, La, hnRNPK, hnRNPI, YBX1, and ELAVL1. Notably, YRNAs may be derived from miRNAs and piRNAs; in particular, Y4sRNA-3p and Y5sRNA-3p in humans are also called piR-hsa-32167 and piR-hsa-116589, respectively. In addition, EV-enclosed YRNAs are detectable in blood plasma, and YRNA ratios are potential biomarkers for inflammatory diseases, including atherosclerosis. YsRNAs are released by apoptotic macrophages into the blood of patients with coronary artery disease (CAD) and are potential biomarkers of foam cell apoptosis for monitoring atherosclerosis pathogenesis. Circulating YsRNAs are also present in EVs of platelets. Interestingly, gut microbes, which play a key role in the gut-heart axis and atherosclerosis progression, also express YRNAs and YsRNAs. Therefore, the gut microbiota may regulate the gut-heart axis and atherosclerosis progression via these YRNAs and YsRNAs. This review focuses on recent advances in our understanding of the potential roles and diagnostic values of YRNAs and YsRNAs in atherosclerosis and identifies new therapeutic and diagnostic targets for atherosclerosis.