Identification of Long Noncoding RNAs Involved in Differentiation and Survival of Vascular Smooth Muscle Cells.

Long noncoding RNAs (lncRNAs) have recently been implicated in many pathophysiological cardiovascular processes, including vascular remodeling and atherosclerosis. However, the functional role of lncRNAs in the differentiation, proliferation, and apoptosis of vascular smooth muscle cells (VSMCs) is largely unknown. In this study, differentially expressed lncRNAs in synthetic and contractile human VSMCs were screened using RNA sequencing. Among the seven selected lncRNAs, the expression of , , and was upregulated, whereas the expression of , , , and was reduced upon VSMC differentiation. We focused on the and lncRNAs and showed that their knockdown significantly reduced the expression of smooth muscle contractile marker genes (, , and ). Furthermore, was found to regulate cell proliferation and apoptosis through Akt/mTOR signaling, and affect Notch signaling, which is a key regulator of the contractile phenotype of VSMCs. Taken together, we identified novel lncRNAs involved in VSMC proliferation and differentiation and as a multifunctional regulator for vascular homeostasis and associated diseases.