Atherosclerosis (AS) is the main aetiology of coronary heart disease, cerebral infarction and peripheral vascular disease in humans. Long-noncoding RNA (LincRNA)-p21 has been reported to participate in the development of AS. Therefore, this study was designed to investigate the mechanism of LincRNA-p21 on suppressing the development of AS. We fed ApoE^−/− mice with a high-fat diet to induce an AS mouse model where the lesion area of AS and the extent of lipid deposition were measured. The binding of LincRNA-p21 and miR-221 or miR-221 and SIRT1 was measured using a dual luciferase reporter gene assay and RIP. Following loss- and gain- function assays, CCK8, EdU, Transwell assay and scratch test were performed to determine the biological processes of human aortic endothelial cells (HAECs). miR-221 was highly expressed while SIRT1 was poorly expressed in AS. LincRNA-p21 acted as a sponge for miR-221. miR-221 targeted and negatively regulated the expression of SIRT1. LincRNA-p21 promoted the deacetylation of Pcsk9 by SIRT1 by competitively binding to miR-221, whereby promoting HAEC proliferation, migration and tube formation. In conclusion, LincRNA-p21 acted as a molecular sponge for miR-221 to promote deacetylation of the promoter region of Pcsk9 by SIRT1, therefore preventing the development of AS.

中文翻译：

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LincRNA-p21 通过调节 miR-221/SIRT1/Pcsk9 轴减轻动脉粥样硬化进展

动脉粥样硬化（AS）是人类冠心病、脑梗塞和外周血管疾病的主要病因。据报道，长链非编码 RNA (LincRNA)-p21 参与了 AS 的发展。因此，本研究旨在探讨LincRNA-p21抑制AS发展的机制。我们喂了 ApoE ^-/-高脂饮食小鼠诱导建立 AS 小鼠模型，测量 AS 病变面积和脂质沉积程度。使用双荧光素酶报告基因测定和 RIP 测量 LincRNA-p21 和 miR-221 或 miR-221 和 SIRT1 的结合。在进行损失和获得功能测定后，进行 CCK8、EdU、Transwell 测定和划痕测试以确定人主动脉内皮细胞 (HAEC) 的生物学过程。miR-221 在 AS 中高表达，而 SIRT1 低表达。LincRNA-p21 充当 miR-221 的海绵。miR-221 靶向并负调控 SIRT1 的表达。LincRNA-p21 通过与 miR-221 竞争性结合来促进 SIRT1 对 Pcsk9 的去乙酰化，从而促进 HAEC 增殖、迁移和管形成。综上所述，