The protease inhibitor E64d improves ox-LDL-induced endothelial dysfunction in human aortic endothelial cells

被引：13

作者：

Chen, Min ^{[1
]}

Ren, Lina ^{[2
]}

Meng, Yanyan ^{[1
]}

Shi, Liye ^{[2
]}

Chen, Ling ^{[2
]}

Yu, Bo ^{[3
,4
]}

Wu, Qianqian ^{[1
]}

Qi, Guoxian ^{[2
]}

机构：

[1] China Med Univ, Affiliated Hosp 1, Dept Cardiol, Shenyang 110001, Liaoning, Peoples R China

[2] China Med Univ, Affiliated Hosp 1, Dept Geriatr, Shenyang 110001, Liaoning, Peoples R China

[3] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Heilongjiang, Peoples R China

[4] Harbin Med Univ, Minist Educ, Key Lab Myocardial Ischemia, Harbin 150086, Heilongjiang, Peoples R China

来源：

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY | 2018年 / 96卷 / 02期

基金：

中国国家自然科学基金;

关键词：

E64d; endothelial dysfunction; ox-LDL; autophagy; HAECs; atherosclerosis; oxidative stress; LOW-DENSITY-LIPOPROTEIN; SIGNALING ADAPTER; VASCULAR-DISEASE; CATHEPSIN-B; AUTOPHAGY; P62; APOPTOSIS; INVITRO; STRESS; IMPACT;

D O I：

10.1139/cjpp-2017-0016

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis. E64d, a cysteine protease inhibitor, blocks the elastolytic activity of cathepsin essential for vascular matrix remodeling and reduces neurovascular endothelial apoptosis. The objective of this study was to investigate the effects and the underling mechanisms of E64d on ox-LDL-induced endothelial dysfunction in human aortic endothelial cells (HAECs). HAECs were treated with various concentrations of ox-LDL (0-200 mg/L) for 24 h with or without E64d. The results showed that E64d attenuated ox-LDL-induced increase in soluble intercellular adhesion molecule-1 (sICAM-1) concentration and reduction in endothelial nitric oxide synthase (eNOS) expression, prevented ox-LDL-induced reduction in cell viability and migration ability of HAECs. E64d decreased the protein expression of cathepsin B (CTSB), Beclin 1, and microtubuleassociated protein light chain 3 (LC3)-II, but not p62. LC3 puncta and autophagosome formation were also reduced by E64d in HAECs. Moreover, E64d decreased the production of MDA and increased the activity of SOD. The results showed that E64d ameliorated ox-LDL-induced endothelial dysfunction in HAECs.

引用

页码：120 / 127

页数：8

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