Wang X, Athayde N, Trudinger B
Department of Obstetrics and Gynaecology, University of Sydney at Westmead Hospital, Sydney, New South Wales, Australia.
BJOG. 2006 Jun;113(6):683-7. doi: 10.1111/j.1471-0528.2006.00928.x.
To seek evidence of early vascular injury in the placental villous microcirculation in placental insufficiency identified by a high-resistance umbilical Doppler study by examining for expression of fibroblast growth factor receptor-1 (FGFR-1), its transcription factor, early growth response factor-1 (Egr-1) and plasma fibroblast growth factor-2 (FGF-2).
Case-control study.
University teaching hospital.
Placentas and umbilical vein blood were collected at delivery from 12 women with normal pregnancy delivered at term and 14 with placental vascular disease defined by an abnormal umbilical artery Doppler study.
Microvascular endothelial cells were isolated from fresh human placentas using collagenase digestion and Dynabeads coated with monoclonal antibody against CD31. RNA was extracted from the isolated endothelial cells. The messenger RNA (mRNA) expression of FGFR-1 and Egr-1 production were assessed by reverse transcription polymerase chain reaction and factored relative to 18S ribosomal RNA. To confirm that FGF-2 was playing a significant role in this microvascular endothelial cell injury in the placenta, we also measured the soluble fraction of FGF-2 in fetal plasma from same groups of pregnancies using an enzyme-linked immunosorbent assay.
Microvascular endothelial cells expression of Egr-1mRNA, FGFR-1 mRNA and presence of soluble FGF-2 in fetal plasma.
The soluble level of FGF-2 in the fetal placental circulation from pregnancy with placental vascular disease was increased when compared with normal pregnancy (median 10.15 pg/ml and interquartile range 5.34-21.83 pg/ml versus 4.46 pg/ml and 3.69-5.66 pg/ml; P < 0.05). Microvascular endothelial cells from the placental villi with placental vascular disease showed upregulation of both FGFR-1 mRNA expression (median 0.72 and interquartile range 0.40-1.64 versus 0.34 and 0.19-0.71; P<0.05) and Egr-1 expression (median 0.79 and interquartile range 0.27-1.86 versus 0.23 and 0.17-0.67; P<0.05) in comparison with normal pregnancy.
Endothelial cells from the placental villi are upregulated for expression of Egr-1 transcription factor gene in placental vascular disease. The FGFR-1 activation and increase in FGF-2 in the fetal circulation are known to be very early features of the response of endothelium to injury. Egr-1 is a promoter of many key pathophysiologically relevant target genes, which influence the development of subsequent vascular lesions. This change may occur before the pathological features recognised on microscopy.
通过检测成纤维细胞生长因子受体-1（FGFR-1）及其转录因子早期生长反应因子-1（Egr-1）的表达以及血浆成纤维细胞生长因子-2（FGF-2），寻找高阻力脐动脉多普勒检查所确定的胎盘功能不全时胎盘绒毛微循环早期血管损伤的证据。
病例对照研究。
大学教学医院。
分娩时从12例足月正常妊娠妇女和14例脐动脉多普勒检查异常所定义的胎盘血管疾病妇女中采集胎盘和脐静脉血。
使用胶原酶消化法和包被抗CD31单克隆抗体的磁珠从新鲜人胎盘中分离微血管内皮细胞。从分离的内皮细胞中提取RNA。通过逆转录聚合酶链反应评估FGFR-1的信使核糖核酸（mRNA）表达和Egr-1的产生，并相对于18S核糖体RNA进行标准化。为证实FGF-2在胎盘微血管内皮细胞损伤中起重要作用，我们还使用酶联免疫吸附测定法测量了同一组妊娠胎儿血浆中FGF-2的可溶性部分。
微血管内皮细胞中Egr-1 mRNA、FGFR-1 mRNA的表达以及胎儿血浆中可溶性FGF-2的存在情况。
与正常妊娠相比，胎盘血管疾病妊娠胎儿胎盘循环中FGF-2的可溶性水平升高（中位数分别为10.15 pg/ml，四分位间距为5.34 - 21.83 pg/ml，而正常妊娠为4.46 pg/ml，3.69 - 5.66 pg/ml；P<0.05）。胎盘血管疾病胎盘绒毛的微血管内皮细胞中FGFR-1 mRNA表达上调（中位数分别为0.72，四分位间距为0.40 - 1.64，而正常妊娠为0.34，0.19 - 0.71；P<0.05），Egr-1表达也上调（中位数分别为0.79，四分位间距为0.27 - 1.86，而正常妊娠为0.23，0.17 - 0.67；P<0.05）。
胎盘血管疾病时胎盘绒毛的内皮细胞中Egr-1转录因子基因表达上调。已知胎儿循环中FGFR-1的激活和FGF-2的增加是内皮细胞对损伤反应的非常早期的特征。Egr-1是许多关键病理生理相关靶基因的启动子，影响后续血管病变的发展。这种变化可能在显微镜下识别的病理特征出现之前就已发生。
