Wang Xin, Athayde Neil, Trudinger Brian
Department of Obstetrics and Gynaecology, University of Sydney at Westmead Hospital, Sydney, Australia.
Am J Obstet Gynecol. 2004 Mar;190(3):596-601. doi: 10.1016/j.ajog.2003.09.021.
Fetal growth restriction is associated with an abnormal umbilical artery Doppler study. A vascular disease is present in the fetal umbilical placental microcirculation. We hypothesized that the local production of factors that are injurious to microvessel endothelium is responsible for this vascular disease and that endothelial cell activation is a feature of this. Because the expression of the cell adhesion molecules is associated with endothelial cell activation, we isolated endothelial cells from the microvessels of the umbilical placenta and examined them for evidence of gene expression of cell adhesion molecules.
Endothelial cells from the microcirculation of human placenta were isolated and purified with collagenase digestion and extraction with superparamagnetic beads that were coated with monoclonal antibody against CD31. Microvessel endothelial cells were isolated from the placentae of 13 women with a normal pregnancy and delivery at term and 10 placentas with umbilical placental vascular disease that was defined by abnormal umbilical artery Doppler study. Total RNA was extracted from isolated endothelial cells. The messenger RNA expressions of cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule-1) were assessed by semiquantitative reverse transcription-polymerase chain reaction.
Microvessel endothelial cells from the fetal placentae of pregnancies that were complicated by umbilical placental vascular disease showed an enhanced expression of intercellular adhesion molecule-1 messenger RNA (2.12+/-0.45 vs 0.92+/-0.25) and platelet endothelial cell adhesion molecule-1 messenger RNA (4.29+/-0.87 vs 2.41+/-0.42) in comparison to normal pregnancies. There was no significant difference in expression of vascular cell adhesion molecule-1 messenger RNA (1.55+/-0.37 vs 1.68+/-0.38).
We have shown that vascular disease in the fetal umbilical placental circulation is associated with an increase in the expression of intercellular adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 by microvessel endothelial cells. We postulate that locally released factors cause injury and activation to microvessel endothelial cells. In this regard, the process in the fetus is similar to that of atherothrombotic vascular disease of later life.
胎儿生长受限与脐动脉多普勒检查异常相关。胎儿脐胎盘微循环存在血管疾病。我们推测，对微血管内皮细胞有害的因子的局部产生是这种血管疾病的原因，且内皮细胞活化是其特征之一。由于细胞黏附分子的表达与内皮细胞活化相关，我们从脐胎盘微血管中分离出内皮细胞，并检测它们是否有细胞黏附分子基因表达的证据。
用胶原酶消化并用包被有抗CD31单克隆抗体的超顺磁性珠提取法分离并纯化人胎盘微循环中的内皮细胞。从13例足月正常妊娠并分娩的妇女的胎盘以及10例经脐动脉多普勒检查异常定义为脐胎盘血管疾病的胎盘中分离微血管内皮细胞。从分离出的内皮细胞中提取总RNA。通过半定量逆转录-聚合酶链反应评估细胞黏附分子（细胞间黏附分子-1、血管细胞黏附分子-1和血小板内皮细胞黏附分子-1）的信使RNA表达。
与正常妊娠相比，合并脐胎盘血管疾病的妊娠胎儿胎盘中的微血管内皮细胞显示细胞间黏附分子-1信使RNA（2.12±0.45对0.92±0.25）和血小板内皮细胞黏附分子-1信使RNA（4.29±0.87对2.41±0.42）表达增强。血管细胞黏附分子-1信使RNA表达无显著差异（1.55±0.37对1.68±0.38）。
我们已表明，胎儿脐胎盘循环中的血管疾病与微血管内皮细胞中细胞间黏附分子-1和血小板内皮细胞黏附分子-1表达增加相关。我们推测局部释放的因子会导致微血管内皮细胞损伤和活化。在这方面，胎儿的过程与晚年的动脉粥样硬化血栓形成性血管疾病相似。
