Inhibition of angiotension II type 1 receptor reduced human endothelial inflammation induced by low shear stress
Inhibition of angiotension II type 1 receptor reduced human endothelial inflammation induced by low shear stress
复制标题
DOI：
10.1016/j.yexcr.2017.08.030
复制
发表时间：
2017-11-15
影响因子：
3.7
通讯作者：
Chen, Shaoliang
中科院分区：
文献类型：
--
作者：
Chao, Yuelin;Zhu, Linlin;Chen, Shaoliang
低切应力（LSS）诱导的内皮炎症是动脉粥样硬化发展的基础。然而，LSS诱导的炎症的机制还没有很好地理解。血管紧张素II 1型受体（AT 1 R）是肾素-血管紧张素系统的一个组成部分，参与动脉粥样硬化斑块的进展。本研究的目的是研究AT 1 R在LSS诱导的内皮激活中的作用。使用免疫组织化学，我们注意到与这些小鼠的降主动脉相比，C57 BL/6小鼠主动脉弓内曲中AT 1 R、血管内皮粘附细胞-1（VCAM 1）和细胞间粘附分子-1（ICAM 1）的表达显着增加。Western blotting结果显示，LPS诱导的AT 1 R、ICAM 1和VCAM 1表达的增加具有时间依赖性。然而，这些蛋白质的表达显着废除与AT 1 R拮抗剂氯沙坦（1 μ M）或AT 1 R小干扰RNA（siRNA）的治疗。AT 1 R抑制显著抑制细胞外信号调节激酶1/2（ERK）的上调，这也导致ICAM 1和VCAM 1蛋白表达的减少。这些发现表明LSS通过AT 1 R/ERK信号转导诱导内皮炎症，并且氯沙坦对内皮炎症具有有益作用。
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.