Marini M, Vichi D, Toscano A, Zappoli Thyrion G D, Parretti E, Mello G, Gheri G, Pacini A, Sgambati E
Department of Anatomy, Histology and Forensic Medicine, University of Florence, Policlinic of Careggi, Viale Morgagni 85, 50134 Florence, Italy.
Reprod Fertil Dev. 2007;19(5):641-51. doi: 10.1071/rd06131.
The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) family receptors (VEGFR) in placentas from pregnancies complicated by hypertensive disorders of different clinical severity. Placental tissue from women with gestational hypertension, pre-eclampsia, pre-eclampsia with haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) and normotensive women, as a control group, was examined. Immunohistochemical techniques, reverse transcription-polymerase chain reaction and western blot were used to evaluate receptor expression. In cases with gestational hypertension, as well as in control cases, VEGFR-1 and VEGFR-3 immunoreactivity was detected in all placental components, whereas in placentas from the pre-eclampsia and pre-eclampsia with HELLP syndrome groups, VEGFR-1 and VEGFR-3 immunoreactivity was detected only in some portions of trophoblast and/or some vessels and/or clusters of stromal cells. In the control group, VEGFR-2 immunoreactivity was observed only in the vessels, whereas the hypertensive groups showed VEGF-2 immunoreactivity also in trophoblast and stromal cells. The mRNA levels of the three receptors in the group with gestational hypertension were higher with respect to those in the control group. Placentas from pregnancies with pre-eclampsia showed lowest mRNA expression levels, whereas placentas from women with pre-eclampsia plus HELLP syndrome showed higher mRNA expression levels with respect to the three other groups. Receptor protein levels were lower in pathological cases compared with levels in the control group. These findings demonstrate a dysregulation of placental expression of VEGF family receptors related to the degree of clinical severity of the hypertensive disorder.
本研究的目的是确定血管内皮生长因子(VEGF)家族受体(VEGFR)在不同临床严重程度的妊娠合并高血压疾病患者胎盘组织中的表达情况。研究对象为患有妊娠期高血压、子痫前期、伴有溶血、肝酶升高及血小板减少的子痫前期(HELLP综合征)的孕妇胎盘组织,以及作为对照组的血压正常孕妇的胎盘组织。采用免疫组织化学技术、逆转录-聚合酶链反应和蛋白质印迹法评估受体表达情况。在妊娠期高血压病例以及对照组病例中,VEGFR-1和VEGFR-3免疫反应性在所有胎盘成分中均有检测到,而在子痫前期组和伴有HELLP综合征的子痫前期组胎盘中,VEGFR-1和VEGFR-3免疫反应性仅在滋养层的某些部分和/或某些血管和/或基质细胞簇中检测到。在对照组中,仅在血管中观察到VEGFR-2免疫反应性,而高血压组在滋养层和基质细胞中也显示出VEGF-2免疫反应性。妊娠期高血压组三种受体的mRNA水平高于对照组。子痫前期妊娠的胎盘显示出最低的mRNA表达水平,而患有子痫前期加HELLP综合征的孕妇胎盘相对于其他三组显示出更高的mRNA表达水平。与对照组相比,病理病例中的受体蛋白水平较低。这些发现表明,VEGF家族受体的胎盘表达失调与高血压疾病的临床严重程度相关。