p53-Dependent LincRNA-p21 Protects Against Proliferation and Anti-apoptosis of Vascular Smooth Muscle Cells in Atherosclerosis by Upregulating SIRT7 via MicroRNA-17-5p.

This study investigated the functional role of p53-lincRNA-p21 in atherosclerosis (AS) by mediating the microRNA-17-5p (miR-17-5p)/SIRT7 axis. Peripheral blood was collected from AS patients, and an ApoE-/- mouse model of AS (AS-M) was induced by high-fat diet. The relationship among p53, lincRNA-p21, miR-17-5p, and SIRT7 was validated, and their effects on AS progression and vascular smooth muscle cell (VSMC) functions were analyzed using gain- and loss-of-function experiments in AS mice and human and mouse VSMCs. p53, lincRNA-p21, and SIRT7 were downregulated, and miR-17-5p was upregulated in AS-M and peripheral blood of AS patients. p53 positively regulated lincRNA-p21, while miR-17-5p, reversely targeted by lincRNA-p21, could target SIRT7. Overexpressing p53, lincRNA-p21, or SIRT7 contributed to impaired proliferation and promoted apoptosis of VSMCs in vitro as well as reducing the vulnerable plaque and lipid accumulation in AS mice. Collectively, p53-dependent lincRNA-p21 expression downregulated miR-17-5p, which consequently protecting against AS progression via SIRT7 elevation. Graphical abstract Collectively, p53-dependent lincRNA-p21 expression downregulated miR-17-5p, whichconsequently protecting against AS progression via SIRT7 elevation.