Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy
Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy
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DOI：
10.1161/hypertensionaha.110.150961
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发表时间：
2010-08-01
期刊：
影响因子：
8.3
通讯作者：
Dechend, Ralf
中科院分区：
文献类型：
--
作者：
Hering, Lydia;Herse, Florian;Dechend, Ralf
肾素-血管紧张素（Ang）系统在胎盘发育过程中起重要作用。肾素-血管紧张素系统的失调在先兆子痫（PE）中是重要的。转人血管紧张素原基因的雌性大鼠与转人肾素基因的雄性大鼠杂交，产生PE综合征，而相反杂交的大鼠则不会。我们用这个模型来研究血管紧张素II在滋养层细胞侵袭中的作用，这在人类PE中是浅的，但在这个模型中更深。我们研究了以下组：PE大鼠，对向交叉大鼠，血管紧张素II输注大鼠（1000 ng/kg/天），和对照组大鼠。Ang II输注仅增加循环Ang II水平（267.82 pg/mL），相反交叉仅影响子宫胎盘Ang II（13.52 fmol/mg蛋白质），PE增加循环（251.09 pg/mL）和子宫胎盘（19.24 fmol/mg蛋白质）Ang II。高循环血管紧张素II模型出现血压和蛋白尿，而其他模型则无此现象。在PE和异性杂交大鼠中滋养细胞侵袭增加，但在Ang II灌注大鼠中没有。相应地，子宫动脉阻力指数增加血管紧张素II注入大鼠，但降低PE大鼠。然后，我们研究了人类滋养层细胞和绒毛外植体从早期妊娠与延时显微镜。局部血管紧张素II剂量依赖性地增加迁移75%，侵袭58%，运动282%。这些数据表明，局部组织血管紧张素II刺激滋养层入侵在体内大鼠和体外人类细胞，迄今为止未被认识的功能。可以想象，胎盘母体部分的组织Ang II的上调代表滋养层侵入和迁移的重要生长因子。（高血压。2010;56：311-318）。
The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II-infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II-infused rats. Correspondingly, uterine artery resistance index increased in Ang II-infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration. (Hypertension. 2010;56:311-318.)