Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
Placenta. 2011 Dec;32(12):956-62. doi: 10.1016/j.placenta.2011.09.020. Epub 2011 Oct 20.
The renin-angiotensin system (RAS) is thought to regulate placentation, however, the expression and localization of RAS pathways in early gestation human placenta is not known. Here we describe the expression of prorenin (REN), (pro)renin receptor (ATP6AP2), angiotensinogen (AGT), angiotensin-converting enzyme 1 and 2 (ACE; ACE2), angiotensin II type 1 and 2 receptors (AGTR1; AGTR2) and angiotensin 1-7 receptor (MAS1), as well as the angiogenic factor, vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1), in early gestation (6-16 weeks) and term (>37 weeks) human placentae. We also describe the location of all of the key RAS proteins in the early gestation placentae. The highest levels of REN, ATP6AP2, AGT, AGTR1 and ACE2 mRNAs were found in early gestation, whereas ACE1 mRNA was highest at term. AGTR2 and MAS1 mRNA expression were low to undetectable in all samples. REN, ATP6AP2 and AGTR1 mRNA levels were correlated with VEGF expression, but not with TGF-β1 mRNA. In early gestation placentae, prorenin, (pro)renin receptor and the angiotensin II type 1 receptor (AT(1)R) were localized to extravillous trophoblast cells, suggesting they play a key role in trophoblast migration. ACE2 in syncytiotrophoblasts could regulate release of Ang 1-7 into the maternal circulation contributing to the vasodilation of the maternal vasculature. ACE was only found in fetal vascular endothelium and may specifically target the growing fetal placental vessels. Because REN, ATP6AP2 and AGTR1 show strong correlations with expression of VEGF this pathway is likely to be important in placental angiogenesis.
肾素-血管紧张素系统（RAS）被认为可以调节胎盘的形成，然而，在早期妊娠人类胎盘中 RAS 途径的表达和定位尚不清楚。在这里，我们描述了前肾素（REN）、（前）肾素受体（ATP6AP2）、血管紧张素原（AGT）、血管紧张素转换酶 1 和 2（ACE；ACE2）、血管紧张素 II 型 1 和 2 受体（AGTR1；AGTR2）和血管紧张素 1-7 受体（MAS1），以及血管生成因子血管内皮生长因子（VEGF）和转化生长因子-β1（TGF-β1）在早期妊娠（6-16 周）和足月（>37 周）胎盘的表达。我们还描述了所有关键 RAS 蛋白在早期妊娠胎盘的位置。REN、ATP6AP2、AGT、AGTR1 和 ACE2 mRNA 的水平在早期妊娠时最高，而 ACE1 mRNA 在足月时最高。AGTR2 和 MAS1 mRNA 在所有样本中表达均低至无法检测。REN、ATP6AP2 和 AGTR1 mRNA 水平与 VEGF 表达相关，但与 TGF-β1 mRNA 无关。在早期妊娠胎盘，前肾素、（前）肾素受体和血管紧张素 II 型 1 受体（AT1R）定位于绒毛外滋养层细胞，表明它们在滋养层细胞迁移中发挥关键作用。合体滋养层细胞中的 ACE2 可以调节 Ang 1-7 释放到母体循环中，有助于母体血管的扩张。ACE 仅在胎儿血管内皮中发现，可能专门针对正在生长的胎儿胎盘血管。由于 REN、ATP6AP2 和 AGTR1 与 VEGF 的表达呈强相关，因此该途径可能在胎盘血管生成中非常重要。
