Inhibition of angiotension II type 1 receptor reduced human endothelial inflammation induced by low shear stress

被引：26

作者：

Chao, Yuelin ^{[1
]}

Zhu, Linlin ^{[1
]}

Qu, Xinliang ^{[1
]}

Zhang, Junxia ^{[1
]}

Zhang, Junjie ^{[1
]}

Kong, Xiangquan ^{[1
]}

Gu, Yue ^{[1
]}

Pu, Jiangqin ^{[1
]}

Wu, Wen ^{[1
]}

Ye, Peng ^{[1
]}

Luo, Jie ^{[1
]}

Yang, Hongfeng ^{[1
]}

Chen, Shaoliang ^{[1
]}

机构：

[1] Nanjing Med Univ, Nanjing Hosp 1, Dept Cardiol, 68 Changle Rd, Nanjing, Jiangsu, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2017年 / 360卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Low shear stress; Angiotensin II type 1 receptor; Inflammation; Mechanotransduction; NF-KAPPA-B; OXIDATIVE STRESS; DEFICIENT MICE; LESION SIZE; CELLS; EXPRESSION; ATHEROSCLEROSIS; ACTIVATION; ADHESION; SYSTEM;

D O I：

10.1016/j.yexcr.2017.08.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Low shear stress (LSS)-induced endothelial inflammation is the basis for the development of atherosclerosis. However, the mechanism underlying LSS-induced inflammation is not well understood. The angiotensin II type 1 receptor (AT1R), a component of the renin-angiotensin system, participates in atherosclerotic plaque progression. The aim of this study was to investigate the role of AT1R in LSS-induced endothelial activation. Using immunohistochemistry, we noted significant increases in AT1R, vascular endothelial adhesion cell-1 (VCAM1), and intercellular adhesion molecule-1 (ICAM1) expression in the inner curvature of the aortic arch in C57BL/6 mice compared to the descending aorta in these mice. Moreover, western blotting revealed that these LSS-induced increases in AT1R, ICAM1 and VCAM1 expression were time dependent. However, the expression of these proteins was significantly abolished by treatment with the AT1R antagonist Losartan (1 mu M) or AT1R small interfering RNA (siRNA). AT1R inhibition significantly suppressed extracellular signal-regulated kinase 1/2 (ERK) upregulation, which also resulted in decreases in ICAM1 and VCAM1 protein expression. These findings demonstrate that LSS induces endothelial inflammation via AT1R/ERK signaling and that Losartan has beneficial effects on endothelial inflammation.

引用

页码：94 / 104

页数：11

共 31 条

[1]

Context-dependent Cooperation between Nuclear Factor κB (NF-κB) and the Glucocorticoid Receptor at a TNFAIP3 Intronic Enhancer [J].