Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells
Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells
复制标题
阿托伐他汀通过 lncRNA NEXN-AS1/NEXN 通路抑制人血管内皮细胞焦亡
DOI：
10.1016/j.atherosclerosis.2019.11.033
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发表时间：
2020-01-01
期刊：
影响因子：
5.3
通讯作者：
Zheng, Lei
中科院分区：
文献类型：
--
作者：
Wu, Li-Mei;Wu, Shao-Guo;Zheng, Lei
背景和目的：许多临床试验表明，他汀类药物对动脉粥样硬化的保护作用不依赖于降胆固醇能力。另有证据表明，细胞程序性死亡--上睑下垂可能参与动脉粥样硬化的形成，但他汀类药物对上睑下垂的影响及其机制有待进一步研究。方法：通过实时定量聚合酶链式反应和Western印迹分析，探讨阿托伐他汀对人血管内皮细胞上睑下垂的影响及其机制。结果：阿托伐他汀以浓度和时间依赖的方式上调长非编码RNA(LncRNA)NEXN-AS1和NEXN在mRNA和蛋白水平的表达。阿托伐他汀通过降低典型炎症体途径生物标志物NLRP3、caspase-1、GSDMD、IL-1β和IL-18在mRNA和蛋白水平的表达水平来抑制下垂。阿托伐他汀对NEXN-AS1和NEXN表达的促进作用可被lncRNA NEXN-AS1或NEXN所抑制，其抑制作用也可被下调ncRNA NEXN-AS1或干扰NEXN所抵消。结论：阿托伐他汀通过抑制ncRNA NEXN-AS1-NEXN途径调节嗜热症，为进一步阐明阿托伐他汀促进非降脂抗动脉粥样硬化作用的机制提供了新的思路，为逆转动脉粥样硬化提供了新方向。
Background and aims: Many clinical trials have demonstrated that statins convey protective effects against atherosclerosis independent of cholesterol-lowering capacities. Other evidence indicates that pyroptosis, a type of programmed cell death, is likely involved in atherosclerosis, but the effects and mechanisms of statins on pyroptosis must be further revealed.Methods: Here, we explored the effects and mechanisms of atorvastatin on pyroptosis in human vascular endothelial cells by quantitative real-time polymerase chain reaction and Western blot analyses.Results: Atorvastatin upregulated long non-coding RNA (lncRNA) NEXN-AS1 and the expression of NEXN at both the mRNA and protein levels in a concentration- and time-dependent manner. Atorvastatin inhibited pyroptosis by decreasing the expression levels of the canonical inflammasome pathway biomarkers NLRP3, caspase-1, GSDMD, IL-1 beta, and IL-18 at both the mRNA and protein levels. The promotion effects of atorvastatin on NEXN-AS1 and NEXN expression could be significantly abolished by knockdown of lncRNA NEXN-AS1 or NEXN, and its inhibitory effects on pyroptosis were also markedly offset by knock-down of lncRNA NEXN-AS1 or interference of NEXN.Conclusions: These results demonstrated that atorvastatin regulated pyroptosis via the lncRNA NEXN-AS1-NEXN pathway, which provides a new insight into the mechanism of how atorvastatin promotes non-lipid-lower effects against the development of atherosclerosis and gives new directions on how to reverse atherosclerosis.