Mary Sheon, Kulkarni Mahesh J, Malakar Dipankar, Joshi Sadhana R, Mehendale Savita S, Giri Ashok P
Division of Biochemical Sciences, CSIR-National Chemical Laboratory , Homi Bhabha Road, Pune, Maharashtra 411008, India.
Sciex , 121 Udyog Vihar, Gurgaon, Haryana 122015, India.
J Proteome Res. 2017 Feb 3;16(2):1050-1060. doi: 10.1021/acs.jproteome.6b00955. Epub 2017 Jan 26.
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.
子痫前期是一种高血压疾病,其特征为妊娠20周后新发高血压(收缩压>140 mmHg和舒张压>90 mmHg)及蛋白尿。该疾病是多因素的,起源于胎盘形成异常。通过无凝胶蛋白质组学技术比较血压正常(n = 25)和子痫前期(n = 25)患者的胎盘蛋白质组,共鉴定出胎盘中2145种蛋白质,其中180种差异表达(>1.3倍,p < 0.05)。生物学过程的基因本体富集分析表明,差异表达的蛋白质属于多种生理过程,如血管生成、细胞凋亡、氧化应激、缺氧和胎盘发育,这些过程与子痫前期的病理生理学有关。通过多反应监测分析在血浆中监测了一些差异表达的蛋白质,结果显示子痫前期患者在妊娠26 - 30周时载脂蛋白A-I和A-II增加(2倍,p < 0.01),而触珠蛋白和血红素结合蛋白在妊娠26 - 30周以及40周/分娩时下降(1.8倍,p < 0.01)。本研究为子痫前期的病理生理学提供了蛋白质组学见解。可进一步评估已鉴定的候选蛋白质,以开发与子痫前期发病机制相关的潜在生物标志物。