Furuya Mitsuko, Kurasawa Kentaro, Nagahama Kiyotaka, Kawachi Kae, Nozawa Akinori, Takahashi Tsuneo, Aoki Ichiro
Department of Pathology, Yokohama City University, Graduate School of Medicine, Yokohama 236-0004, Japan.
J Pregnancy. 2011;2011:123717. doi: 10.1155/2011/123717. Epub 2011 Mar 3.
The placenta plays a central role in governing local circulatory system that mediates maternal condition and fetal growth. In early gestational phases, the placenta exerts properties of invasion and neovascularization for successful placentation. Extravillous invasive trophoblasts replace uterine endometrial vasculature and establish local blood pathway to obtain oxygen and nutrients from the mother. In later phases, the placenta promotes villous angiogenesis and vascular maturation that are finely controlled by angiogenic and antiangiogenic molecules. Among various molecules involved in placental neovascularization, vascular endothelial growth factor receptors (VEGFRs) and angiotensin II receptor type 1 (AT1) mediate important signaling pathways for maternal circulatory system and fetal growth. VEGFR1 and VEGFR2 are functional receptors for placental growth factor (PlGF) and VEGF, respectively, and PlGF-VEGFR1 and VEGF-VEGFR2 interactions are disturbed in many preeclamptic patients by excess amount of soluble form of VEGFR1 (also named sFlt1), a natural PlGF/VEGF antagonist. Recent studies have disclosed that excessive sFlt1 production in the placenta and aberrant AT1 signaling in the mother are closely associated with the pathology of preeclampsia and intrauterine growth restriction (IUGR). In this paper, neovascularization of the placenta and pathological events associated with disrupted balance between angiogenic and antiangiogenic signaling in preeclampsia are discussed.
胎盘在调节介导母体状况和胎儿生长的局部循环系统中起着核心作用。在妊娠早期，胎盘发挥侵袭和新血管形成的特性以实现成功着床。绒毛外侵袭性滋养层细胞取代子宫子宫内膜血管，并建立局部血液通路以从母体获取氧气和营养物质。在后期，胎盘促进绒毛血管生成和血管成熟，这受到血管生成和抗血管生成分子的精细调控。在参与胎盘新血管形成的各种分子中，血管内皮生长因子受体（VEGFRs）和血管紧张素II 1型受体（AT1）介导了对母体循环系统和胎儿生长至关重要的信号通路。VEGFR1和VEGFR2分别是胎盘生长因子（PlGF）和血管内皮生长因子（VEGF）的功能性受体，在许多子痫前期患者中，PlGF-VEGFR1和VEGF-VEGFR2的相互作用因过量的可溶性VEGFR1（也称为sFlt1，一种天然的PlGF/VEGF拮抗剂）而受到干扰。最近的研究表明，胎盘中过量的sFlt1产生以及母体中异常的AT1信号传导与子痫前期和宫内生长受限（IUGR）的病理密切相关。本文讨论了胎盘的新血管形成以及子痫前期中血管生成和抗血管生成信号失衡相关的病理事件。
