Li-Mei Wu1, Shao-Guo Wu2, Fei Chen3, Qian Wu4, Chang-Meng Wu4, Chun-Min Kang5, Xin He6, Ru-Yi Zhang4, Zhi-Feng Lu4, Xue-Heng Li4, Yuan-Jun Xu4, Li-Min Li6, Li Ding4, Huan-Lan Bai4, Xue-Hui Liu2, Yan-Wei Hu7, Lei Zheng8. 1. Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou, 510620 , 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, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 5. Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510280, China. 6. Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510120, China. 7. Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, 510623, China. Electronic address: ywhu0618@smu.edu.cn. 8. Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: nfyyzhenglei@smu.edu.cn.
Abstract
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-1β, 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.
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-1β, 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.