Sharma Saurabh, Yadav Suniti, Chandiok Ketaki, Sharma Radhey Shyam, Mishra Vandana, Saraswathy Kallur Nava
Bioresources & Environmental Biotechnology Laboratory, Department of Environmental Studies, University of Delhi, Delhi, India.
Molecular Anthropology Laboratory, Department of Anthropology, University of Delhi, Delhi, India.
PeerJ. 2019 Feb 14;7:e6321. doi: 10.7717/peerj.6321. eCollection 2019.
Metabolic syndrome (MeS), a constellation of metabolic adversities, and history of miscarriage make women at a higher risk for cardiovascular diseases (CVDs). However, molecular evidence indicating a link between the two phenotypes (history of miscarriage and MeS) among women would offer an opportunity to predict the risk factor for CVDs at an early stage. Thus, the present retrospective study attempts to identify the proteins signatures (if any) to understand the connection between the history of miscarriage and MeS.
Age-matched 80 pre-menopausal women who were not on any medical intervention or drugs were recruited from a Mendelian population of the same gene pool. Recruited women were classified into four groups-(a) Group A-absolute cases with history of miscarriage and MeS, (b) Group B-absolute controls without any history of miscarriage and MeS, (c) Group C-cases with MeS but lack any history of miscarriage, (d) Group D-cases with history of miscarriage but lack MeS. Differentially expressed proteins in plasma samples of women from four groups were identified using 2-D gel electrophoresis and mass spectrometry.
Three case groups (A, C, and D) showed 18 differentially expressed proteins. Nearly 60% of proteins (11/18) were commonly dysregulated in Group C (only with MeS) and Group D (only with miscarriage history). Nearly 40% of proteins (7/18) were commonly dysregulated in the three case groups (Groups A, C, and D), indicating a shared pathophysiology. Four proteins were exclusive but shared by case groups C and D indicating the independent routes for CVDs through MeS or miscarriages. In absolute cases, transthyretin (TTR) showed exclusive upregulation, which was further validated by Western blotting and ELISA. Networking analyses showed the strong association of TTR with haptoglobin, transferrin and ApoA1 hinting toward a cross-talk among these proteins which could be a cause or an effect of TTR upregulation.
The study provides evidence for molecular link between the history of miscarriage and MeS through a putative role of TTR. However, longitudinal follow-up studies with larger sample size would further help to demonstrate the significance of TTR and other targeted proteins in risk stratification and the onset of CVDs.
代谢综合征（MeS）是一系列代谢方面的不利情况，而流产史会使女性患心血管疾病（CVDs）的风险更高。然而，表明女性中这两种表型（流产史和MeS）之间存在联系的分子证据，将为在早期阶段预测CVDs的风险因素提供机会。因此，本回顾性研究试图确定蛋白质特征（如果有的话），以了解流产史与MeS之间的联系。
从同一基因库的孟德尔人群中招募了80名年龄匹配的未接受任何医学干预或药物治疗的绝经前女性。招募的女性被分为四组：（a）A组——有流产史和MeS的绝对病例；（b）B组——无任何流产史和MeS的绝对对照；（c）C组——有MeS但无任何流产史的病例；（d）D组——有流产史但无MeS的病例。使用二维凝胶电泳和质谱法鉴定四组女性血浆样本中差异表达的蛋白质。
三个病例组（A、C和D）显示出18种差异表达的蛋白质。近60%的蛋白质（11/18）在C组（仅患有MeS）和D组（仅有无流产史）中共同失调。近40%的蛋白质（7/18）在三个病例组（A、C和D组）中共同失调，表明存在共同的病理生理学。四种蛋白质是C组和D组特有的，但两组共有，表明通过MeS或流产导致CVDs的独立途径。在绝对病例中，转甲状腺素蛋白（TTR）表现出特有的上调，通过蛋白质印迹法和酶联免疫吸附测定进一步验证。网络分析显示TTR与触珠蛋白、转铁蛋白和载脂蛋白A1有很强的关联，提示这些蛋白质之间存在相互作用，这可能是TTR上调的原因或结果。
该研究通过TTR的假定作用为流产史与MeS之间的分子联系提供了证据。然而，更大样本量的纵向随访研究将进一步有助于证明TTR和其他靶向蛋白质在风险分层和CVDs发病中的意义。
