Atorvastatin inhibits pyroptosis through the lncRNA NEXN-AS1/NEXN pathway in human vascular endothelial cells
| Autor: | Xue-Hui Liu, Ru-Yi Zhang, Chun-Min Kang, Lei Zheng, Li-Min Li, Xin He, Yan-Wei Hu, Li Ding, Chang-Meng Wu, Huan-Lan Bai, Zhi-Feng Lu, Xue-Heng Li, Yuan-Jun Xu, Shao-Guo Wu, Limei Wu, Fei Chen, Qian Wu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death Inflammasomes Atorvastatin Blotting Western 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Western blot Pyroptosis medicine Humans Cells Cultured Gene knockdown Messenger RNA medicine.diagnostic_test Chemistry Anticholesteremic Agents Microfilament Proteins Endothelial Cells Inflammasome Atherosclerosis 030104 developmental biology Gene Expression Regulation Cancer research RNA Long Noncoding lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine Signal Transduction medicine.drug |
| Zdroj: | Atherosclerosis. 293:26-34 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/j.atherosclerosis.2019.11.033 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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