Long Non-coding RNA PEBP1P2 Suppresses Proliferative VSMCs Phenotypic Switching and Proliferation in Atherosclerosis

Long non-coding RNAs (lncRNAs) play a crucial role in the growth of vascular smooth muscle cells (VSMCs), which dysfunction is closely associated with the initiation and progression of cardiovascular diseases (CVDs). Abnormal phenotypic switching and proliferation of VSMCs constitute a significant event of the progression of atherosclerosis. The present study identified a novel lncRNA-PEBP1P2 serves as a valuable regulator of VSMCs in phenotypic transformation and proliferation. The expression of PEBP1P2 was remarkably decreased in proliferating VSMCs and pathological arteries from the balloon injury model of rats. Furthermore, we found that PEBP1P2 represses proliferation, migration and dedifferentiation during phenotype switching in VSMCs induced by PDGF-BB. Mechanistically, CDK9 was confirmed to be the direct target of PEBP1P2, which was proved to mediate phenotypic switching and proliferation of VSMCs and rescued by PEBP1P2. Then, we explored the clinical significance as we observed the decreased expression of PEBP1P2 in the serum of coronary heart disease (CHD) patients, and human advanced carotid atherosclerotic plaques. Finally, PEBP1P2 overexpression distinctly suppressed neointima formation and VSMCs phenotypic switching in vivo. Taken together, PEBP1P2 inhibits proliferation and migration in VSMCs by directly binding to CDK9, implying that it may be a promising therapeutic target for the treatment of proliferative vascular diseases.