Angiotensin II induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells
Angiotensin II induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells
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DOI：
10.1016/j.atherosclerosis.2010.05.020
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发表时间：
2010-09-01
期刊：
影响因子：
5.3
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Han, Chunjie;Liu, Juntian;Li, Ming
背景：动脉粥样硬化是一种血管炎症性疾病。作为一种炎症细胞因子，C 反应蛋白 (CRP) 参与动脉粥样硬化形成。尽管已知血管紧张素 II (AngII) 会引起血管内皮细胞 (VEC) 的炎症反应，但没有直接证据表明 AngII 通过 CRP 对 VEC 产生促炎作用。本研究主要探讨AngII对人主动脉内皮细胞(HAECs)CRP表达及信号通路的影响。方法与结果:分别采用RT-PCR和Western blot鉴定mRNA和蛋白表达。通过荧光显微镜观察活性氧（ROS）。结果表明，AngII 以时间和浓度依赖性方式显着增加 HAEC 中 CRP 的 mRNA 和蛋白表达。抗IL-1β和抗IL-6中和抗体不影响AngII诱导的CRP表达。氯沙坦降低了 HAEC 中 AngII 诱导的 CRP mRNA 和蛋白水平表达。氯沙坦和 TIFA 减少了 AngII 刺激的 ROS 生成，抗氧化剂 NAC 完全消除了 HAEC 中 AngII 诱导的 CRP 表达。进一步研究表明，氯沙坦、NAC、PD98059、SP600125显着抑制ERK1/2和JNK磷酸化，PD98059、SP600125、PDTC完全拮抗AngII诱导的HAECs中CRP表达。结论：本研究表明AngII具有通过AT1-ROS-ERK1/2和AT1-ROS-ERK1/2诱导HAECs中CRP表达的能力。 JNK-NF-kappa B 信号通路，加强了对 AngII 促炎和促动脉粥样硬化作用的理解。 (C) 2010 Elsevier Ireland Ltd. 保留所有权利。
Background: Atherosclerosis is an inflammatory disease in the vessel. As an inflammatory cytokine, C-reactive protein (CRP) participates in atherogenesis. Although angiotensin II (AngII) is known to evoke inflammatory response in vascular endothelial cells (VECs), there is no direct evidence to demonstrate the proinflammatory effect of AngII on VECs through CRP. The present study focused on effect of AngII on CRP expression and the signal pathway in human aortic endothelial cells (HAECs).Methods and results: mRNA and protein expression was identified by RT-PCR and Western blot, respectively. Reactive oxygen species (ROS) were observed by a fluorescence microscope. The results showed that AngII significantly increased mRNA and protein expression of CRP in HAECs in time- and concentration-dependent ways. Anti-IL-1 beta and anti-IL-6 neutralizing antibodies did not affect AngII induced CRP expression. Losartan reduced AngII-induced CRP expression in mRNA and protein levels in HAECs. Losartan and TIFA decreased AngII-stimulated ROS generation, and antioxidant NAC completely abolished AngII-induced CRP expression in HAECs. The further study indicated that losartan, NAC, PD98059, SP600125 significantly inhibited ERK1/2 and JNK phosphorylation, and PD98059, SP600125, PDTC completely antagonized AngII-induced CRP expression in HAECs.Conclusions: The present study demonstrates that AngII has ability to induce CRP expression in HAECs through AT1-ROS-ERK1/2 and JNK-NF-kappa B signal pathway, which strengthens understanding of the proinflammatory and proathroscerotic actions of AngII. (C) 2010 Elsevier Ireland Ltd. All rights reserved.