The counterregulating role of ACE2 and ACE2-mediated angiotensin 1-7 signaling against angiotensin II stimulation in vascular cells
The counterregulating role of ACE2 and ACE2-mediated angiotensin 1-7 signaling against angiotensin II stimulation in vascular cells
复制标题
DOI：
10.1038/hr.2010.147
复制
发表时间：
2010-11-01
影响因子：
5.4
通讯作者：
Rakugi, Hiromi
中科院分区：
文献类型：
--
作者：
Hayashi, Norihiro;Yamamoto, Koichi;Rakugi, Hiromi
为了阐明内源性血管紧张素转换酶2(ACE2)及其裂解产物Ang 1-7在动脉粥样硬化刺激血管细胞中的作用，我们研究了ACE2和Ang 1-7受体Mas的药理抑制对Ang II刺激的细胞反应的影响。免疫印迹法检测细胞外信号调节激酶(ERK)1/2的磷酸化，WST法检测细胞外信号调节激酶1/2(ERK)1/2的磷酸化水平，荧光微板法检测PKH67标记的单核细胞与内皮细胞(ECs)的粘附率。血管紧张素转换酶II、血管紧张素Ⅱ1型受体(AT1)阻断剂奥美沙坦、血管紧张素转换酶抑制剂DX600、D-丙氨酸-血管紧张素转换酶拮抗剂D-丙氨酸-血管紧张素转换酶1-7(D-Ala7-Ang1-7)或二者联合作用后，血管紧张素转换酶1/2(ERK1/2)磷酸化，血管紧张素转换酶(SMC)增殖和单核细胞与EC的黏附均被奥美沙坦阻断。DX600的预处理不会加速或仅略微加速这些细胞反应。然而，当通过AT1的Ang II信号被奥美沙坦减少时，DX600的额外处理显著减弱了奥美沙坦的一些作用。同样，D-ALA可降低奥美沙坦对Ang II刺激的抑制作用。血管细胞内源性血管紧张素转换酶2可能通过上调血管紧张素转换酶1-7信号途径参与对抗血管紧张素转换酶II介导的细胞反应。高血压研究(2010年)3311821185；DOI：10.1038/hr.2010.147；2010年8月12日在线发布
To clarify the role of endogenous angiotensin (Ang)-converting enzyme 2 (ACE2) and its cleavage product, Ang 1-7, in the atherogenic stimulation of vascular cells, we investigated the effect of pharmacological inhibition of ACE2 and Mas, an Ang 1-7 receptor, on cellular responses against Ang II stimulation. We measured extracellular signal-regulated kinase (ERK) 1/2 phosphorylation by western blot, smooth muscle cell (SMC) proliferation by WST assay and the adhesion of monocytes labeled with PKH67 to endothelial cells (ECs) by fluorescence microplate reader. Cells were pretreated with Ang 1-7, olmesartan (Ang II type 1 receptor (AT1) blocker), DX600 (ACE2 inhibitor), D-Ala7-Ang1-7 (D-Ala; Mas antagonist), or combinations of treatments before the application of Ang II. Treatment with Ang II increased phosphorylated ERK 1/2 of SMC and EC, proliferation of SMC and adhesion of monocyte to EC, which were blocked by olmesartan. Pretreatment with DX600 either did not accelerate or only slightly accelerated these cellular responses. However, when Ang II signaling through AT1 was reduced by olmesartan, the additional treatment with DX600 significantly blunted some of the effect of olmesartan. Similarly, pretreatment with D-Ala reduced the inhibitory effect of olmesartan in response to Ang II stimulation. Endogenous ACE2 in vascular cells may contribute to counteracting the Ang II-mediated cellular response partly by upregulating the Ang 1-7 signaling through Mas. Hypertension Research (2010) 33, 1182-1185; doi:10.1038/hr.2010.147; published online 12 August 2010