Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3 inflammasome activation in LPS-induced vascular injury

Acta Pharmaceutica Sinica. B
Xing ZhouYang Chen

Abstract

The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide (2 μg/mL) and administrated by 0.1-2 mmol/L aspirin. The wild type mice were stimulated with LPS (100 μg/kg/day), and 1 h later treated with aspirin (12.5, 62.5, or 125 mg/kg/day) and dexamethasone (0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in vitro in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of the endothelial tight junction protein zonula occludens-1/2 (ZO...Continue Reading

Citations

Jun 5, 2020·Journal of Receptor and Signal Transduction Research·Zengjun XieLiang Zhao
Jun 13, 2020·Free Radical Research·Zhengjun WangLi Liu
Apr 7, 2020·Journal of Receptor and Signal Transduction Research·Wenjun LiangMingxia Yang
Sep 20, 2020·Cell Death & Disease·Baochen BaiXian-Ming Chu
Jan 30, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Fengyang LiYunman Li
Jan 27, 2021·International Journal of Molecular Sciences·Carmen De MiguelSantiago Cuevas
Jan 12, 2021·Frontiers in Oncology·Kai-Jun LuoJean X Jiang
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Wan-Li JiangSong-Ping Xie
Feb 12, 2021·International Journal of Molecular Sciences·Alison DominguesValérie Nivet-Antoine

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Methods Mentioned

BETA
immunoprecipitation assay
protein assay
ELISA
transfection
fluorescence microscopy
confocal microscopy
gene knockdown

Software Mentioned

Image Pro Plus
Image J

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