Long noncoding RNA p21 enhances autophagy to alleviate endothelial progenitor cells damage and promote endothelial repair in hypertension through SESN2/AMPK/TSC2 pathway

• DOI: 10.1016/j.phrs.2021.105920
• Publication Date: 2021-10-01T10:31:35Z
• Authors: Chao Li; Lin Lin; Lei Zhang; Ran Xu; Xiaoqing Chen; Jingkang Ji; Yunlun Li
• Keywords: Male; 0301 basic medicine; Angiotensin II; Nuclear Proteins; AMP-Activated Protein Kinases; Middle Aged; beta-Galactosidase; 3. Good health; 03 medical and health sciences; Cell Movement; Rats, Inbred SHR; Hypertension; Tuberous Sclerosis Complex 2 Protein; Autophagy; Cell Adhesion; Animals; Humans; Female; RNA, Long Noncoding; Rats, Wistar; Aged; Endothelial Progenitor Cells

Vascular damage of hypertension has been the focus of hypertension treatment, and endothelial progenitor cells (EPCs) play an important role in the repair of vascular endothelial damage. Functional damage and decreased number of EPCs are observed in the peripheral circulation of hypertensive patients, but its mechanism is not yet elucidated. Here, we show that the number of EPCs in hypertensive patients is significantly lower than that of normal population, and the cell function decreases with a higher proportion of EPCs at later stages. A decrease in autophagy is responsible for the senescence and damage of EPCs induced by AngII. Moreover, lncRNA-p21 plays a critical regulator role in EPCs' senescence and dysfunction. Furthermore, lncRNA-p21 activates SESN2/AMPK/TSC2 pathway by promoting the transcriptional activity of p53 and enhances autophagy to protect against AngII-induced EPC damage. The data provide evidence that a reversal of decreased autophagy serves as the protective mechanism of EPC injury in hypertensive patients, and lncRNA-p21 is a new therapeutic target for vascular endothelial repair in hypertension.