Study of Pathophysiology of Preeclampsia : The Prediction and Prevention

胎盘抗血管生成和抗氧化因子的增加被认为在子痫前期（PE）的发病机制中起着至关重要的作用。在妊娠后期发生PE的妇女中，这些胎盘的改变被认为始于妊娠早期，当时外滋养细胞重塑为螺旋动脉的内皮细胞。我们已经观察到在1^<st>妊娠滋养细胞中基因表达的体内改变，这些孕妇注定会在以后发展为PE。本研究通过绒毛膜绒毛取样（chorionic vilous sampling， CVS）前瞻性采集胎儿核型分析时的绒毛滋养细胞组织样本，并评估这些基因的mRNA表达。结果显示，妊娠后期发生PE的孕妇CVS组织中FLT-1、ENG、VEGF和TGF-β1的表达水平显著升高，而PlGF、HO-1和超氧化物歧化酶（SOD）的表达水平较低。这些发现表明，与血管生成和抗氧化应激相关的基因的更多表达在PE的发病机制中起着至关重要的作用，并且测量这些因子在母体血液中的表达可能有助于预测PE的发病。胎儿/胎盘RNA在母体血液的血浆或细胞隔室中循环，这使得一些有前途的方法得以发展，用于无创评估胎盘功能。因此，为了证明通过母体血液中游离RNA或细胞RNA预测PE的可能性，我们评估了15 - 20周孕妇血液中FLT-1、ENG、VEGF等7个基因的表达。我们发现，通过判别分析模型，这组血浆RNA在妊娠15-20周的PE预测率为84%，假阳性率为5%。在母体血液中的细胞RNA中也检测到相同的结果。接下来，为了确定一组细胞信使RNA标记物的组合分布是否可以在妊娠1^<st bb0妊娠早期检测到PE，我们评估了11至14周孕妇的细胞RNA水平。结果发现，ENG、FLT-1和TGF-β1的值高于预期，PlGF和胎盘蛋白13的值低于预期。在妊娠11-14周，细胞RNA的预测率为72.3%，假阳性率为5%。这些发现表明，分析从妊娠早期孕妇获得的细胞游离RNA或细胞RNA是评估胎盘功能变化的非常有前途的方法。少

Increased production of placental anti-angiogenic and anti-oxidative factors are considered to play a crucial role in the pathogenesis of preeclampsia(PE). These placental alterations in women who develop PE in later gestation are thought to begin during the first trimester when extravillous trophoblasts remodel into the endothelial cells of the spiral arteries. We have observed the in vivo alteration of gene expressions in the 1^<st> trimester-trophoblasts from pregnant women who destined to develop PE later. This study prospectively collected tissue samples of villous trophoblasts at the time of fetal karyotype analysis through chorionic villous sampling (CVS), and assessed the mRNA expression of these genes. The results revealed that the expression levels of FLT-1, ENG, VEGF, and TGF-β1 were significantly higher in the CVS tissues from pregnant women who later developed PE whereas the levels of PlGF, HO-1, and superoxide dismutase (SOD) were lower. These findings suggest that the ex … More pression of genes associated with angiogenesis and anti-oxidant stress have crucial roles in the pathogenesis of PE, and that measurement of the expression of these factors in the maternal blood may enable the prediction of the onset of PE.Fetal/placental RNA circulates in the plasma or cellular compartment of maternal blood and it has enabled the development of several promising approaches for non-invasive evaluation of placental function. Therefore, to prove the possibility of predicting PE by cell-free or cellular RNA in maternal blood, the expression of 7 genes including FLT-1, ENG and VEGF were assessed in the blood of pregnant women between 15 and 20 weeks. We found that this panel of plasma RNA allows an 84% prediction rate for PE with a 5% false positive rate at gestational week 15-20 by means of a discriminant analysis model. The same results were detected in the cellular RNA in maternal blood. Next, to determine whether the combined distribution of a panel of cellular messenger RNA markers at 1^<st> trimester can detect PE long before onset, we assessed cellular RNA levels in the pregnant women between 11 and 14 weeks. As results, higher values than expected were found for ENG, FLT-1, and TGF-β1, and lower values were found for PlGF and placental protein 13. The panel of cellular RNA allows an 72.3% prediction rate for PE with a 5% false positive rate at gestational week 11-14.These findings indicate that the analyses of cell-free or cellular RNA obtained from pregnant women at early gestation are highly promising methods to evaluate alterations in placental function. Less