CAD increases the long noncoding RNA in small extracellular vesicles and regulates endothelial cell function via vesicular shuttling.

Long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators of cardiovascular disease. However, the expression pattern of circulating extracellular vesicle (EV)-incorporated lncRNAs in patients with coronary artery disease (CAD) is still poorly investigated. A human lncRNA array revealed that certain EV-lncRNAs are significantly dysregulated in CAD patients. Circulating small EVs (sEVs) from patients with (n = 30) or without (n = 30) CAD were used to quantify (also known as antisense RNA 1 []), , , and RNA levels. (p = 0.002) and (p = 0.02) were significantly increased in patients with CAD, compared to non-CAD patients. Fluorescent labeling and quantitative real-time PCR of sEVs demonstrated that functional was transported into the recipient cells. Mechanistically, the RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK), interacts with , regulating its loading into sEVs. Knockdown of abrogated the EV-mediated effects on endothelial cell (EC) migration, proliferation, tube formation, and sprouting. Angiogenesis-related gene profiling showed that the expression of vascular endothelial growth factor A () RNA was significantly increased in EV recipient cells. Protein stability and RNA immunoprecipitation indicated that the -hnRNPK axis regulates the stability and binding of mRNA to hnRNPK. Loss of in EVs abolished the EV-mediated promotion of VEGFA gene and protein expression. Intercellular transfer of EV-incorporated promotes a pro-angiogenic phenotype via a VEGFA-dependent mechanism.