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

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.

• Authors: Li-Mei Wu, Shao-Guo Wu, Fei Chen, Qian Wu, Chang-Meng Wu, Chun-Min Kang, Xin He, Ru-Yi Zhang, Zhi-Feng Lu, Xue-Heng Li, Yuan-Jun Xu, Li-Min Li, Li Ding, Huan-Lan Bai, Xue-Hui Liu, Yan-Wei Hu, Lei Zheng
• Journal: Atherosclerosis (Atherosclerosis) Vol. 293 Pg. 26-34 (01 2020) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 31830726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anticholesteremic Agents
• Inflammasomes
• Microfilament Proteins
• NEXN protein, human
• RNA, Long Noncoding
• Atorvastatin

Topics

• Anticholesteremic Agents (pharmacology)
• Atherosclerosis (drug therapy, genetics, metabolism)
• Atorvastatin (pharmacology)
• Blotting, Western
• Cells, Cultured
• Endothelial Cells (cytology, metabolism)
• Gene Expression Regulation
• Humans
• Inflammasomes (metabolism)
• Microfilament Proteins (genetics, metabolism)
• Pyroptosis (drug effects, genetics)
• RNA, Long Noncoding (genetics)
• Signal Transduction (drug effects)