Department of Cardiology, Shenzhen Baoan District People's Hospital, Shenzhen 518101, Guangdong, People's Republic of China.
Inflamm Res. 2013 Feb;62(2):219-28. doi: 10.1007/s00011-012-0571-2. Epub 2012 Dec 12.
Endothelial dysfunction plays an important role in all stages of atherosclerosis and is characterized by an increased proinflammatory response. This study investigated the effect of angiotensin (1-7) on angiotensin II (Ang II)-mediated inflammation in endothelial cells (ECs) and uncovered its molecular mechanism.
Real-time PCR and western blot analysis were used to determine lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. Ang II treatment induced inflammation, as measured by the production of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, by activating nuclear factor-κB (NF-κB) in ECs. Ang II also induced LOX-1 expression in human ECs and rabbit aortic ECs. LOX-1 played an essential role in Ang II-mediated inflammation because Ang II antagonists or small interference RNA significantly decreased Ang II-induced VCAM-1 production. LOX-1 overexpression enhanced Ang II-mediated inflammation. LOX-1 mediated Ang II-induced inflammation by inducing NF-κB DNA-binding activity. Angiotensin (1-7) inhibited LOX-1 expression and diminished Ang II-mediated inflammation in ECs.
Our findings suggest that angiotensin (1-7) prevents Ang II-induced inflammation by inhibiting LOX-1 mRNA and protein expression in ECs and may represent a novel pleiotropic effect of angiotensin (1-7).
内皮功能障碍在动脉粥样硬化的所有阶段都起着重要作用，其特征是促炎反应增加。本研究探讨了血管紧张素（1-7）对血管内皮细胞（ECs）中血管紧张素 II（Ang II）介导的炎症的影响，并揭示了其分子机制。
实时 PCR 和 Western blot 分析用于确定凝集素样氧化低密度脂蛋白受体-1（LOX-1）的表达。Ang II 处理通过激活核因子-κB（NF-κB）在 ECs 中诱导炎症，如血管细胞黏附分子-1 和单核细胞趋化蛋白-1 的产生所测量。Ang II 还在人 ECs 和兔主动脉 ECs 中诱导 LOX-1 表达。LOX-1 在 Ang II 介导的炎症中起着至关重要的作用，因为 Ang II 拮抗剂或小干扰 RNA 显著降低了 Ang II 诱导的 VCAM-1 产生。LOX-1 过表达增强了 Ang II 介导的炎症。LOX-1 通过诱导 NF-κB DNA 结合活性介导 Ang II 诱导的炎症。血管紧张素（1-7）抑制 LOX-1 的表达，并减弱 ECs 中 Ang II 介导的炎症。
我们的研究结果表明，血管紧张素（1-7）通过抑制 ECs 中 LOX-1 mRNA 和蛋白表达来预防 Ang II 诱导的炎症，这可能代表血管紧张素（1-7）的一种新的多效作用。
