Possible Involvement of Angiotensin-Converting Enzyme 2 and Mas Activation in Inhibitory Effects of Angiotensin II Type 1 Receptor Blockade on Vascular Remodeling
Possible Involvement of Angiotensin-Converting Enzyme 2 and Mas Activation in Inhibitory Effects of Angiotensin II Type 1 Receptor Blockade on Vascular Remodeling
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DOI：
10.1161/hypertensionaha.112.191452
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发表时间：
2012-07-01
期刊：
影响因子：
8.3
通讯作者：
Horiuchi, Masatsugu
中科院分区：
文献类型：
--
作者：
Iwai, Masaru;Nakaoka, Hirotomo;Horiuchi, Masatsugu
我们探讨了血管紧张素转换酶2 （ACE2）、血管紧张素-(1-7)和Mas激活在血管紧张素II型1受体阻断介导的血管重构衰减中的作用。在小鼠股动脉周围放置聚乙烯袖带诱导血管损伤。袖带放置后，野生型小鼠的ACE2和Mas mRNA水平均明显降低，而ACE mRNA未发生变化。ACE2和Mas的免疫染色主要在介质中观察到，在损伤动脉中减少。给药血管紧张素-(1-7)减少袖带放置后新内膜的形成，而给药[D-Ala(7)]血管紧张素-(1-7)，一种Mas拮抗剂，增加新内膜的形成。与这些结果一致，我们还证明，在ACE2基因敲除小鼠中，袖带放置诱导的新内膜形成进一步增加。在血管紧张素II 1a型受体敲除小鼠中，损伤动脉中ACE2和Mas的mRNA表达和免疫染色均高于野生型小鼠，新内膜形成较少。用血管紧张素II型受体阻滞剂奥美沙坦治疗野生型小鼠，也观察到损伤动脉中ACE2表达增加。这些结果表明，ace2 -血管紧张素-(1-7)- mas轴的激活至少部分参与了血管紧张素II型1受体阻断对血管重塑的有益作用。（中国高血压杂志，2012;60:137-144）
We explored the roles of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7), and Mas activation in angiotensin II type 1 receptor blockade-mediated attenuation of vascular remodeling. Vascular injury was induced by polyethylene-cuff placement around the mouse femoral artery. After cuff placement, the mRNA level of both ACE2 and Mas was markedly decreased in wild-type mice, whereas ACE mRNA was not changed. Immunostaining of ACE2 and Mas was observed mainly in the media and was reduced in the injured artery. Administration of angiotensin-(1-7) decreased neointimal formation after cuff placement, whereas administration of [ D-Ala(7)] angiotensin-(1-7), a Mas antagonist, increased it. Consistent with these results, we also demonstrated that neointimal formation induced by cuff placement was further increased in ACE2 knockout mice. In angiotensin II type 1a receptor knockout mice, mRNA expression and immunostaining of ACE2 and Mas in the injured artery were greater, with less neointimal formation than in wild-type mice. Increased ACE2 expression in the injured artery was also observed by treatment of wild-type mice with an angiotensin II type 1 receptor blocker, olmesartan. These results suggested that activation of the ACE2-angiotensin-(1-7)-Mas axis is at least partly involved in the beneficial effects of angiotensin II type 1 receptor blockade on vascular remodeling. (Hypertension. 2012; 60: 137-144.) circle Online Data Supplement