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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
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.
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页码:182 / 188
页数:7
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