Department of Cardiology, Peking University People's Hospital, Beijing, China.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):642-6. doi: 10.1016/j.bbrc.2012.11.098. Epub 2012 Dec 3.
Angiotensin II (Ang II) and Angiotensin-(1-7) (Ang-(1-7)) are key effector peptides in the renin-angiotensin system. Increased circulatory Ang II level is associated with the development of hypertension and atherosclerosis, whereas Ang-(1-7) is a counter-regulatory mediator of Ang II which appears to be protective against cardiovascular disease. However, whether Ang-(1-7) regulates the action of Ang II on vascular endothelial cells (EC) remains unclear. We investigated the effects of Ang II and Ang-(1-7) in the context of atherogenesis, specifically endothelial cell VCAM-1 expression that is implicated in early plaque formation. The results show that Ang II increased VCAM-1 mRNA expression and protein displayed on EC surface, while Ang-(1-7) alone exerted no effects. However, Ang-(1-7) significantly suppressed Ang II-induced VCAM-1 expression. Ang-(1-7) also inhibited the Ang II-induced VCAM-1 promoter activity driven by transcription factor NF-KappaB. Furthermore, immunofluorescence assay and ELISA showed that Ang II facilitated the nuclear translocation of NF-kappaB in ECs, and this was attenuated by the presence of Ang-(1-7). The inhibitory effects of Ang-(1-7) on Ang II-induced VCAM-1 promoter activity and NF-kappaB nuclear translocation were all reversed by the competitive antagonist of Ang-(1-7) at the Mas receptor. Our results suggest that Ang-(1-7) mediates its affects on ECs through the Mas receptor, and negatively regulates Ang II-induced VCAM-1 expression by attenuating nuclear translocation of NF-kappaB.
血管紧张素 II（Ang II）和血管紧张素-(1-7)（Ang-(1-7)）是肾素-血管紧张素系统中的关键效应肽。循环中 Ang II 水平升高与高血压和动脉粥样硬化的发展有关，而 Ang-(1-7) 是 Ang II 的一种反向调节介质，似乎对心血管疾病具有保护作用。然而，Ang-(1-7) 是否调节 Ang II 对血管内皮细胞（EC）的作用尚不清楚。我们研究了 Ang II 和 Ang-(1-7) 在动脉粥样硬化形成中的作用，特别是内皮细胞 VCAM-1 的表达，这与早期斑块形成有关。结果表明，Ang II 增加了 VCAM-1 mRNA 的表达和 EC 表面的蛋白表达，而 Ang-(1-7) 单独作用时则没有影响。然而，Ang-(1-7) 显著抑制了 Ang II 诱导的 VCAM-1 表达。Ang-(1-7) 还抑制了转录因子 NF-KappaB 驱动的 Ang II 诱导的 VCAM-1 启动子活性。此外，免疫荧光和 ELISA 检测显示，Ang II 促进了 NF-kappaB 在 EC 中的核转位，而 Ang-(1-7) 的存在则减弱了这一过程。Ang-(1-7) 对 Ang II 诱导的 VCAM-1 启动子活性和 NF-kappaB 核转位的抑制作用均被 Ang-(1-7) 在 Mas 受体上的竞争性拮抗剂所逆转。我们的研究结果表明，Ang-(1-7) 通过 Mas 受体介导其对 EC 的影响，并通过减弱 NF-kappaB 的核转位来负调节 Ang II 诱导的 VCAM-1 表达。
