Impaired mitochondrial fusion, autophagy, biogenesis and dysregulated lipid metabolism is associated with preeclampsia
Impaired mitochondrial fusion, autophagy, biogenesis and dysregulated lipid metabolism is associated with preeclampsia
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线粒体融合、自噬、生物发生和脂质代谢失调与先兆子痫相关
DOI：
10.1016/j.yexcr.2017.07.029
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发表时间：
2017-10-01
影响因子：
3.7
通讯作者：
Zhang, Hua
中科院分区：
文献类型：
--
作者：
Zhou, Xiaobo;Han, Ting-Li;Zhang, Hua
先兆子痫（PE）是一种妊娠并发症，通过新发高血压和蛋白尿来诊断。 PE 的病因尚不清楚；然而，越来越多的证据表明线粒体损伤是发病机制之一。因此，我们的目的是研究线粒体在PE发生过程中的功能。使用气相色谱-质谱 (GC-MS) 分析先兆子痫 (n = 11) 和正常 (n = 11) 胎盘中的线粒体代谢组。进行学生 t 检验和受试者工作特征 (ROC) 曲线，以确定两组之间哪些线粒体代谢物存在显着差异。 Pathway Activity Profiling (PAPi) R 软件包用于预测哪些代谢途径受 PE 影响。进行蛋白质印迹分析以鉴定与线粒体修复调节相关的候选蛋白。 GC-MS 分析表明，在严重 PE (sPE) 患者的胎盘中观察到 38 种代谢物水平较高，2 种代谢物水平较低。五种脂肪酸的 ROC 曲线下面积高于 90%。此外，我们还揭示了 sPE 中线粒体动力学、自噬和生物发生的异常调节。我们的发现表明，sPE 中脂质代谢受损可能是由线粒体功能障碍引起的，从而揭示了对该疾病病因学的新见解。
Preeclampsia(PE) is a pregnancy complication that is diagnosed by the new onset of hypertension and proteinuria. The etiology of PE remains unclear; however, growing evidence indicates that mitochondrial impairment contributes to the pathogenesis. Therefore, we aim to investigate the function of mitochondria in the development of PE. The mitochondrial metabolome in preeclamptic (n = 11) and normal (n = 11) placentas were analyzed using Gas chromatography-mass spectrometry (GC-MS). Student's t-tests and receiver operating characteristic (ROC) curves were conducted to determine which mitochondrial metabolites differed significantly between the two groups. The Pathway Activity Profiling (PAPi) R package was used to predict which metabolic pathways were affected by PE. Western blot analysis was performed to identify the candidate proteins which were associated with mitochondria' repair regulation. GC-MS analysis demonstrated that higher levels of 38 metabolites and lower levels of 2 metabolites were observed in the placenta of patients with severe PE (sPE). Five fatty acids had an area under the ROC curve above 90%. Furthermore, we revealed abnormal regulation of mitochondria' dynamics, autophagy, and biogenesis in sPE. Our discoveries indicate that the compromised lipid metabolism in sPE may result from dysfunctional mitochondria, thus revealing new insights into the etiology of the disease.