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Plasma Proteome Profiling of Coronary Artery Disease Patients: Downregulation of Transthyretin—An Important Event
Mediators of Inflammation ( IF 4.4 ) Pub Date : 2020-11-10 , DOI: 10.1155/2020/3429541
Monu 1 , Rupsi Kharb 1, 2 , Ankita Sharma 1 , Monu Kumar Chaddar 1 , Rakesh Yadav 3 , Prachi Agnihotri 1 , Anand Kar 4 , Sagarika Biswas 1
Affiliation  

Coronary artery disease (CAD) is a prevalent chronic inflammatory cardiac disorder. An early diagnosis is likely to help in the prevention and proper management of this disease. As the study of proteomics provides the potential markers for detection of a disease, in the present investigation, attempt has been made to identify disease-associated differential proteins involved in CAD pathogenesis. For this study, a total of 200 selected CAD patients were considered, who were recruited for percutaneous coronary intervention (PCI) treatment. The proteomic analysis was performed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF MS/MS. Samples were also subjected to Western blot analysis, enzyme-linked immunosorbent assay (ELISA), peripheral blood mononuclear cells isolation immunofluorescence (IF) analysis, analytical screening by fluorescence-activated cell sorting (FACS), and in silico analysis. The representative data were shown as of at least three experiments. A total of 19 proteins were identified. Among them, the most abundant five proteins (serotransferrin, talin-1, alpha-2HS glycoprotein, transthyretin (TTR), fibrinogen-α chain) were found to have altered level in CAD. Serotransferrin, talin-1, alpha-2HS glycoprotein, and transthyretin (TTR) were found to have lower level, whereas fibrinogen-α chain was found to have higher level in CAD plasma compared to healthy, confirmed by Western blot analysis. TTR, an important acute phase transport protein, was validated low level in 200 CAD patients who confirmed to undergo PCI treatment. Further, in silico and in vitro studies of TTR indicated a downexpression of CAD in plasma as compared to the plasma of healthy individuals. Lower level of plasma TTR was determined to be an important risk marker in the atherosclerotic-approved CAD patients. We suggest that the TTR lower level predicts disease severity and hence may serve as an important marker tool for CAD screening. However, further large-scale studies are required to determine the clinical significance of TTR.

中文翻译:


冠状动脉疾病患者的血浆蛋白质组分析:运甲状腺素蛋白下调——一个重要事件



冠状动脉疾病(CAD)是一种流行的慢性炎症性心脏病。早期诊断可能有助于预防和适当管理这种疾病。由于蛋白质组学研究为检测疾病提供了潜在的标记,因此在目前的研究中,已尝试鉴定与 CAD 发病机制相关的疾病相关差异蛋白。在这项研究中,总共考虑了 200 名选定的 CAD 患者,他们被招募来接受经皮冠状动脉介入治疗 (PCI) 治疗。使用二维凝胶电泳 (2-DE) 和 MALDI-TOF MS/MS 进行蛋白质组分析。样品还进行了蛋白质印迹分析、酶联免疫吸附测定 (ELISA)、外周血单核细胞分离免疫荧光 (IF) 分析、荧光激活细胞分选 (FACS) 分析筛选和计算机分析。显示了至少三个实验的代表性数据。总共鉴定出 19 种蛋白质。其中,最丰富的五种蛋白质(血清转铁蛋白、talin-1、α-2HS糖蛋白、运甲状腺素蛋白(TTR)、纤维蛋白原链)被发现在CAD中水平发生改变。通过蛋白质印迹分析证实,与健康人相比,CAD 血浆中血清转铁蛋白、talin-1、α-2HS 糖蛋白和运甲状腺素蛋白 (TTR) 的水平较低,而纤维蛋白原链的水平较高。 TTR 是一种重要的急性期转运蛋白,在 200 名确认接受 PCI 治疗的 CAD 患者中被证实处于低水平。此外,TTR 的计算机模拟和体外研究表明,与健康个体的血浆相比,血浆中 CAD 的表达下调。 较低水平的血浆 TTR 被确定为动脉粥样硬化批准的 CAD 患者的重要风险标志物。我们认为 TTR 较低水平可以预测疾病的严重程度,因此可以作为 CAD 筛查的重要标记工具。然而,还需要进一步的大规模研究来确定 TTR 的临床意义。
更新日期:2020-11-13
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