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.

本研究通过介导 microRNA-17-5p (miR-17-5p)/SIRT7 轴，研究了 p53-lincRNA-p21 在动脉粥样硬化 (AS) 中的功能作用。采集AS患者外周血，通过高脂饮食诱导ApoE ^−/−小鼠AS模型（AS-M）。验证了 p53、lincRNA-p21、miR-17-5p 和 SIRT7 之间的关系，并使用 AS 小鼠的功能获得和丧失实验分析了它们对 AS 进展和血管平滑肌细胞 (VSMC) 功能的影响以及人类和小鼠的 VSMC。 AS-M 和 AS 患者外周血中 p53、lincRNA-p21 和 SIRT7 下调，miR-17-5p 上调。 p53 正向调节 lincRNA-p21，而 lincRNA-p21 反向靶向的 miR-17-5p 可以靶向 SIRT7。过表达 p53、lincRNA-p21 或 SIRT7 会导致体外 VSMC 增殖受损并促进细胞凋亡，并减少 AS 小鼠中的易损斑块和脂质积累。总的来说，p53 依赖性 lincRNA-p21 表达下调 miR-17-5p，从而通过 SIRT7 升高防止 AS 进展。