Tsatsaris Vassilis, Goffin Frederic, Munaut Carine, Brichant Jean-François, Pignon Marie-Rose, Noel Agnes, Schaaps Jean-Pierre, Cabrol Dominique, Frankenne Francis, Foidart Jean-Michel
Department of Obstetrics and Gynecology, Hôpital de la Citadelle, B-4000 Liège, Belgium.
J Clin Endocrinol Metab. 2003 Nov;88(11):5555-63. doi: 10.1210/jc.2003-030528.
Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development.
多种生长因子，如血管内皮生长因子（VEGF）-A和胎盘生长因子（PlGF），参与胎盘血管发育。我们研究了VEGF家族的失调是否可以解释子痫前期特征性的子宫胎盘血管形成缺陷。我们将早发型重度子痫前期或胎儿宫内生长受限的妊娠与正常妊娠进行了比较。收集了母体血浆、胎盘和胎盘床活检组织。对胎盘和胎盘床中VEGF-A、PlGF及其受体的mRNA水平进行了定量分析。检测了母体血浆中VEGF-A、PlGF和可溶性VEGF受体（VEGFR）的水平。在受损妊娠中，VEGF-A和VEGFR-1 mRNA水平升高可能反映了胎盘的缺氧状态。相反，子痫前期患者胎盘床中膜结合型VEGFR-1减少。子痫前期与循环中PlGF水平降低以及总VEGF-A和可溶性VEGFR-1水平升高有关。母体血液中未检测到游离VEGF-A。免疫组织化学研究显示，VEGF-A和PlGF定位于滋养层细胞。总之，我们的结果提示了与子痫前期相关的两种不同的病理生理机制。第一种机制与竞争性可溶性VEGFR-1的过度产生有关，这可能导致VEGF-A和PlGF的作用受到抑制。第二种机制是胎盘床中其膜结合形式（VEGFR-1）的下调，这可能导致子宫胎盘发育缺陷。
