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TMT-Based Quantitative Proteomic Analysis Identification of Integrin Alpha 3 and Integrin Alpha 5 as Novel Biomarkers in Pathogenesis of Acute Aortic Dissection.
BioMed Research International ( IF 2.6 ) Pub Date : 2020-07-02 , DOI: 10.1155/2020/1068402
Lingyu Xing 1 , Yuan Xue 1 , Yilin Yang 1 , Ping Wu 2 , Catherine C L Wong 3 , Haojun Wang 1 , Zhenju Song 1 , Dongwei Shi 1 , Chaoyang Tong 1 , Chenling Yao 1 , Guorong Gu 1
Affiliation  

Background. Acute aortic dissection (AAD) is a devastating cardiovascular disease with a high rate of disability and mortality. This disease often rapidly progresses to fatal multiple organ hypoperfusion, and the incidence has been increasing in recent years. However, the molecular mechanisms have yet to be clarified. This study is aimed at identifying the differential abundance proteins (DAPs) of aortic arch tissues in patients with AAD by proteomics and select possible proteins involved in AAD pathogenesis. Methods. The fresh aortic arch tissues obtained from 5 AAD patients and 1 healthy donor were analyzed by amine-reactive tandem mass tag (TMT) labelling and mass spectrometry; then, the pathological sections of another 10 healthy donors and 20 AAD patients were chosen to verify the proteomic results by immunohistochemistry. Results. Of 809 proteins identified by proteomic analysis, 132 differential abundance proteins (DAPs) were screened, of which 100 proteins were significantly downregulated while 32 upregulated. Among 100 downregulated proteins, two proteins with known function, integrin alpha 3 (ITGA-3) and ITGA-5, were selected as target proteins involved in AAD pathogenesis. Two target DAPs were verified by immunohistochemisty, and the results showed that the integrated option density (IOD) of ITGA-3 and ITGA-5 in AAD patients was significantly lower than that in healthy donors, which were consistent with the proteomic results (). Conclusion. ITGA-3 and ITGA-5 represent novel biomarkers for the pathogenesis of AAD and might be a therapeutic target in the future.

中文翻译:

基于 TMT 的定量蛋白质组学分析鉴定整合素 Alpha 3 和整合素 Alpha 5 作为急性主动脉夹层发病机制中的新型生物标志物。

背景。急性主动脉夹层 (AAD) 是一种毁灭性的心血管疾病,具有很高的致残率和死亡率。该病常迅速发展为致命的多器官灌注不足,近年来发病率呈上升趋势。然而,分子机制尚未阐明。本研究旨在通过蛋白质组学鉴定 AAD 患者主动脉弓组织的差异丰度蛋白 (DAP),并选择可能参与 AAD 发病机制的蛋白质。方法. 对 5 例 AAD 患者和 1 例健康供体的新鲜主动脉弓组织进行胺反应串联质量标签 (TMT) 标记和质谱分析;然后,选择另外10名健康供体和20名AAD患者的病理切片,通过免疫组织化学验证蛋白质组学结果。结果. 在蛋白质组学分析鉴定的 809 种蛋白质中,筛选出 132 种差异丰度蛋白 (DAP),其中 100 种蛋白质显着下调,32 种上调。在 100 种下调的蛋白质中,选择了两种功能已知的蛋白质,整合素 α 3 (ITGA-3) 和 ITGA-5,作为参与 AAD 发病机制的靶蛋白。免疫组化验证了两个靶点DAP,结果显示AAD患者ITGA-3和ITGA-5的综合选择密度(IOD)显着低于健康供者,与蛋白质组学结果一致。)。 结论。ITGA-3 和 ITGA-5 代表了 AAD 发病机制的新型生物标志物,并可能成为未来的治疗靶点。
更新日期:2020-07-02
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