ox-LDL induces endothelial dysfunction by promoting Arp2/3 complex expression

被引：20

作者：

Tang, Yao ^{[1
]}

Zhao, Jianting ^{[1
]}

Shen, Liming ^{[1
]}

Jin, Yiqi ^{[1
]}

Zhang, Zhixuan ^{[1
]}

Xu, Guoxiong ^{[1
]}

Huang, Xianchen ^{[1
]}

机构：

[1] Nanjing Med Univ, Suzhou Hosp Affiliated, Suzhou Municipal Hosp, Vasc Surg, 26 Daoqian St, Suzhou 215002, Jiangsu, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2016年 / 475卷 / 02期

关键词：

Arp2/3; ox-LDL; LOX-1; Rac-1; Endothelial dysfunction; LOW-DENSITY-LIPOPROTEIN; CELL-SHAPE; ACTIN; ATHEROSCLEROSIS; ATHEROGENESIS; ACTIVATION; GAMMA;

D O I：

10.1016/j.bbrc.2016.05.068

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：

Oxidized low-density lipoproteins (ox-LDL) play a critical role in endothelial injury including cytoskeleton reorganization, which is closely related to actin-related protein 2/3 (Arp2/3) complex. The aim of this study was to investigate the role of Arp2/3 complex in ox-LDL-induced endothelial dysfunction. In this study, we found that Arp2 and Arp3 expression was increased under atherosclerotic conditions both in ApoE(-/-) mice and in ox-LDL-stimulated human coronary artery endothelial cells (HCAECs). Arp2/3 complex inhibitor CK666 significantly reduced ox-LDL-induced ROS generation and cytoskeleton reorganization, and increased NO release in HCAECs. Pretreatment with LOX-1- but not CD36-blocking antibody markedly decreased ox-LDL-induced Arp2 and Arp3 expression. Moreover, Rac-1 siRNA remarkably suppressed ox-LDL-stimulated Arp2 and Arp3 expression. Additionally, CK666 reduced endothelial nitric oxide synthase (eNOS) expression and atherosclerotic lesions in ApoE(-/-) mice. Collectively, ox-LDL induces endothelial dysfunction by activating LOX-1/Rac-1 signaling and upregulating Arp2/3 complex expression. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：182 / 188

页数：7

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