Preeclampsia is a pregnancy specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. To reveal the relationship between lipids and preeclampsia, we conduct lipidomic profiling of maternal serums of 44 severe preeclamptic and 20 healthy pregnancies from a multi-ethnic cohort in Hawaii. Correlation network analysis shows that oxidized phospholipids (OxPLs) have increased inter-correlations and connections in preeclampsia, while other lipids, including triacylglycerols (TAGs), have reduced network correlations and connections. Thirty-one lipid species from various lipid classes demonstrate predominantly reductions and causal relationships with preeclampsia. They include phosphatidylglycerol (PG), TAG, diacylglycerol (DAG), phosphatidylcholine (PC), cholesterol esters (CE), phosphatidylethanolamine (PE), sphingomyelin (SM), ceramides (Cer-NS), hexosyl ceramides (HexCer-NS), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and free fatty acid (FFA). Many of these lipids are also selected as important features by a linear discriminant analysis (LDA) classifier with high predictive accuracy (F-1 statistic 0.941 and balanced accuracy 0.88), indicating their potential to serve as biomarkers for severe preeclampsia. Our study supports the hypothesis of a phospholipid (PL) centered, dysregulated lipidomic metabolic atlas. That is, severe preeclampsia may be originated from hypoxia, which induces the accumulation of OxPLs through oxidative stress whereas reduces many other lipids (eg. reduced PCs, TAGs and ceramides). These molecular changes coherently lead to dysregulated biological functions, such as insulin signaling and inflammation/infections. Moreover, the lipid changes may also be responsible for the comorbidity between preeclampsia and gestational diabetes, a clinically known risk factor for preeclampsia.

中文翻译：

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孕妇血液脂质组学分析与严重先兆子痫相关的关键代谢途径相关

子痫前期是妊娠特异性综合征，其特征在于妊娠20周后出现高血压和蛋白尿。为了揭示脂质与先兆子痫之间的关系，我们对来自夏威夷多种族人群的44例严重先兆子痫和20例健康妊娠的孕妇血清进行了脂质组分析。相关网络分析显示，先兆子痫中氧化磷脂（OxPLs）的相互关系和连接增加，而其他脂类，包括三酰基甘油（TAGs），则降低了网络相关性和连接。来自各种脂质类别的31种脂质种类主要表现为先兆子痫的减少和因果关系。它们包括磷脂酰甘油（PG），TAG，二酰甘油（DAG），磷脂酰胆碱（PC），胆固醇酯（CE），磷脂酰乙醇胺（PE），鞘磷脂（SM），神经酰胺（Cer-NS），己糖基神经酰胺（HexCer-NS），溶血磷脂酰胆碱（LPC），溶血磷脂酰乙醇胺（LPE）和游离脂肪酸（FFA）。这些脂质中的许多也被线性判别分析（LDA）分类器选择为重要特征，具有很高的预测准确度（F-1统计量0.941和平衡准确度0.88），表明它们有可能用作严重先兆子痫的生物标志物。我们的研究支持以磷脂（PL）为中心，脂质组代谢图谱失调的假说。也就是说，严重的先兆子痫可能是由缺氧引起的，缺氧通过氧化应激诱导OxPL的积累，同时降低了许多其他脂质（例如，降低的PC，TAG和神经酰胺）。这些分子变化连贯地导致生物学功能失调，例如胰岛素信号传导和炎症/感染。此外，脂质的变化也可能导致先兆子痫和妊娠糖尿病之间的合并症，这是先兆子痫的临床已知危险因素。