Vascular peroxide 1 promotes ox-LDL-induced programmed necrosis in endothelial cells through a mechanism involving β-catenin signaling

Atherosclerosis
Yin-Zhuang ZhangJun Peng

Abstract

Vascular peroxidase 1 (VPO1) plays a key role in mediation of cardiovascular oxidative injury. This study aims to determine whether VPO1 can promote programmed necrosis of endothelial cells and the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 48 h to induce cell injury, which showed an elevation in cell necrosis (reflected by the increased propidium iodide (PI) positive-staining cells, LDH release and decreased cell viability), concomitant with an increase in programmed necrosis-relevant proteins including receptor-interacting protein kinase 1/3 (RIPK1/3), p-RIPK3 and mixed lineage kinase domain like (MLKL); these phenomena were attenuated by necrostatin-1(Nec-1) and RIPK3 siRNA. Meanwhile, VPO1 was up-regulated in ox-LDL-treated endothelial cells accompanied by a decrease in GSK-3β activity and p-β-catenin levels, and an elevation of β-catenin levels; these phenomena were reversed in the presence of VPO1 siRNA or hypochlorous acid (HOCl) inhibitor; replacement of ox-LDL with HOCl could also induce endothelial programmed necrosis and activate the β-catenin signaling; β-catenin inhibitor could also suppress ox-LDL-induced RIPK-...Continue Reading

Citations

May 6, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Yi-Yue ZhangJun Peng
Sep 23, 2020·Nutrients·Tawar QaradakhiAnthony Zulli
Sep 3, 2020·Heart, Lung & Circulation·Mingchang PangLihua Li
Jan 11, 2020·Experimental Eye Research·Jing-Jie PengXiao-Bo Xia
Apr 11, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Huxinyue DuanChunjie Wu
Nov 28, 2021·Molecular Biology Reports·Hongxin XuYing Zhao

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