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Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells

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机构: [1]Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China [2]Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou, 510620 , China [3]Department of Ultrasound, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China [4]Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510280, China [5]Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510120, China [6]Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, 510623, China [7]Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
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关键词: Atorvastatin lncRNA NEXN-AS1 NEXN Pyroptosis NLRP3 caspase-1 GSDMD IL-1 beta IL-18

摘要:
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.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 外周血管病 3 区 心脏和心血管系统
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 外周血管病 3 区 心脏和心血管系统
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出版当年[2018]版:
Q1 PERIPHERAL VASCULAR DISEASE Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
最新[2023]版:
Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Q1 PERIPHERAL VASCULAR DISEASE

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者机构: [1]Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China [2]Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou, 510620 , China
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通讯机构: [1]Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China [6]Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, 510623, China [7]Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China [*1]Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
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