Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress

Drug Design, Development and Therapy
Liwei HangZhiliang Li

Abstract

This study was to investigate the mechanism of inflammatory pathology modification induced by ox-LDL in endothelial cells. In this study, we firstly investigated the efflux of cholesterol of endothelial cells under the treatment of ox-LDL, and cell proliferation, ROS production, cell apoptosis was measured. Further, proteins of ASK1, NLRP3 inflammasomes and endoplasmic reticulum stress response were detected. Afterwards, ASK1 inhibitor (GS-4997) or endoplasmic reticulum stress (ERS) inhibitor (4-PBA) was used to measure the performance of endothelial cells. In this study, endothelial cells were treated with ox-LDLs alone or in combination with a GS-4997 or 4-PBA. Results showed that ox-LDLs attenuated the efflux of cholesterol from endothelial cells in a dose-dependent manner. Ox-LDLs inhibited the proliferation of endothelial cells, and induced their apoptosis and production of reactive oxygen species (ROS). Additionally, ox-LDLs upregulated the levels of phosphorylated ASK1, ERS-related proteins (chop, p-PERK, GRP78, and p-IRE-1), and inflammation-associated proteins (NLRP3, IL-1β, and caspase 1) in endothelial cells. Moreover, we proved that GS-4997 could partly reverse ox-LDL-mediated cell proliferation, apoptosis, ROS prod...Continue Reading

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Citations

Sep 24, 2020·Oxidative Medicine and Cellular Longevity·Shengjie YangSongzi Wang
Nov 6, 2020·Oxidative Medicine and Cellular Longevity·Andrea GonzalezClaudio Cabello-Verrugio
Feb 10, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rui ZhangChangwei Liu
Mar 7, 2021·Biomedicines·Simone PatergnaniAlessandro Rimessi

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Methods Mentioned

BETA
flow cytometry
Assay
ELISA

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