Simvastatin Attenuates H2O2-Induced Endothelial Cell Dysfunction by Reducing Endoplasmic Reticulum Stress

被引：7

作者：

He, Zhigiang ^{[1
]}

He, Xuanhong ^{[1
]}

Liu, Menghan ^{[1
]}

Hua, Lingyue ^{[1
]}

Wang, Tian ^{[1
]}

Liu, Qian ^{[1
]}

Chen, Lai ^{[2
]}

Yan, Nianlong ^{[1
]}

机构：

[1] Nanchang Univ, Coll Basic Med Sci, Dept Biochem & Mol Biol, Nanchang 330006, Jiangxi, Peoples R China

[2] Jiangxi Univ Tradit Chinese Med, Lab Anim Res Ctr Sci & Technol, Nanchang 330004, Jiangxi, Peoples R China

来源：

MOLECULES | 2019年 / 24卷 / 09期

基金：

中国国家自然科学基金;

关键词：

endothelial cell dysfunction; endoplasmic reticulum stress; simvastatin; Wnt; -catenin pathway; OXIDATIVE STRESS; CHOLESTEROL; EXPRESSION; APOPTOSIS; ATHEROSCLEROSIS; PROLIFERATION; ASSOCIATION; METABOLISM; MECHANISMS; RAFTS;

D O I：

10.3390/molecules24091782

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Atherosclerosis is the pathological basis of cardiovascular disease, whilst endothelial dysfunction (ED) plays a primary role in the occurrence and development of atherosclerosis. Simvastatin has been shown to possess significant anti-atherosclerosis activity. In this study, we evaluated the protective effect of simvastatin on endothelial cells under oxidative stress and elucidated its underlying mechanisms. Simvastatin was found to attenuate H2O2-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/-catenin pathway; however, when this pathway was activated by lithium chloride, endothelial dysfunction was clearly enhanced. Further investigation revealed that simvastatin did not alter the expression or phosphorylation of LRP6, but reduced intracellular cholesterol deposition and inhibited endoplasmic reticulum (ER) stress. Inducing ER stress with tunicamycin activated the Wnt/-catenin pathway, whereas reducing ER stress with 4-phenylbutyric acid inhibited it. We hypothesize that simvastatin does not affect transmembrane signal transduction in the Wnt/-catenin pathway, but inhibits ER stress by reducing intracellular cholesterol accumulation, which blocks intracellular signal transduction in the Wnt/-catenin pathway and ameliorates endothelial dysfunction.

引用

页数：14

共 42 条

[1] Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress-Induced Endothelial Dysfunction [J].