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大德路总院检验科大德路总院检验科广东省中医院深圳市中医院深圳医学信息中心[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
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81871701, 81672076, 81572051, 81772244]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2017A030313535, 2017A030313532, 2018A030313533]; Science and Technology Program of Guangzhou [201607010267, 201604020015, 201707010156, 201707010034]; Major Program of Health Care and Innovation of Guangzhou Project [201704020213]
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
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
JCR分区:
出版当年[2018]版:
Q1PERIPHERAL VASCULAR DISEASEQ2CARDIAC & CARDIOVASCULAR SYSTEMS
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
共同第一作者:
通讯作者:
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.
推荐引用方式(GB/T 7714):
Wu Li-Mei,Wu Shao-Guo,Chen Fei,et al.Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells[J].ATHEROSCLEROSIS.2020,293:26-34.doi:10.1016/j.atherosclerosis.2019.11.033.
APA:
Wu, Li-Mei,Wu, Shao-Guo,Chen, Fei,Wu, Qian,Wu, Chang-Meng...&Zheng, Lei.(2020).Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells.ATHEROSCLEROSIS,293,
MLA:
Wu, Li-Mei,et al."Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells".ATHEROSCLEROSIS 293.(2020):26-34