Placental Proteomics Provides Insights into Pathophysiology of Pre-Eclampsia and Predicts Possible Markers in Plasma

Pre-eclampsia
is a hypertensive disorder characterized by the new
onset of hypertension >140/90 mmHg and proteinuria after the 20th
week of gestation. The disorder is multifactorial and originates with
abnormal placentation. Comparison of the placental proteome of normotensive
(n = 25) and pre-eclamptic (n =
25) patients by gel-free proteomic techniques identified a total of
2145 proteins in the placenta of which 180 were differentially expressed
(>1.3 fold, p < 0.05). Gene ontology enrichment
analysis of biological process suggested that the differentially expressed
proteins belonged to various physiological processes such as angiogenesis,
apoptosis, oxidative stress, hypoxia, and placental development, which
are implicated in the pathophysiology of pre-eclampsia. Some of the
differentially expressed proteins were monitored in the plasma by
multiple reaction monitoring analysis, which showed an increase in
apolipoproteins A-I and A-II in gestational weeks 26–30 (2-fold, p < 0.01), while haptoglobin and hemopexin decreased
in gestational weeks 26–30 and week 40/at delivery (1.8 fold, p < 0.01) in pre-eclamptic patients. This study provides
a proteomic insight into the pathophysiology of pre-eclampsia. Identified
candidate proteins can be evaluated further for the development of
potential biomarkers associated with pre-eclampsia pathogenesis.

子痫前期（Pre-eclampsia）是一种高血压性疾病，以妊娠20周后新发高血压（血压＞140/90 mmHg）伴蛋白尿为特征。该疾病为多因素性，起源于胎盘形成异常。研究人员采用无凝胶蛋白质组学技术，对血压正常（n=25）与子痫前期（n=25）患者的胎盘蛋白质组进行比较分析，共在胎盘组织中鉴定出2145种蛋白质，其中180种存在差异表达（表达倍数变化＞1.3，p＜0.05）。对差异表达蛋白开展生物学过程基因本体富集分析后发现，这些蛋白涉及血管生成、细胞凋亡、氧化应激、缺氧及胎盘发育等多种生理过程，而这些过程均与子痫前期的病理生理学机制密切相关。研究人员通过多反应监测分析对血浆中的部分差异表达蛋白进行验证，结果显示，在妊娠26~30周时，子痫前期患者血浆中的载脂蛋白A-I与载脂蛋白A-II水平升高（2倍变化，p＜0.01）；而结合珠蛋白与血红素结合蛋白则在妊娠26~30周及妊娠40周/分娩时水平降低（1.8倍变化，p＜0.01）。本研究为子痫前期的病理生理学机制提供了蛋白质组学视角，所鉴定出的候选蛋白可进一步用于评估与子痫前期发病机制相关的潜在生物标志物开发。