Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
National Centre for Protein Science Shanghai, Shanghai 200032, China.
Biomed Res Int. 2020 Jul 2;2020:1068402. doi: 10.1155/2020/1068402. eCollection 2020.
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.
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.
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 ( < 0.001).
ITGA-3 and ITGA-5 represent novel biomarkers for the pathogenesis of AAD and might be a therapeutic target in the future.
急性主动脉夹层(AAD)是一种破坏性心血管疾病,其残疾和死亡率较高。这种疾病常迅速发展为致命的多器官低灌注,近年来发病率一直在上升。然而,其分子机制尚未阐明。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。
用胺反应串联质量标签(TMT)标记和质谱分析法分析 5 例 AAD 患者和 1 例健康供体的新鲜主动脉弓组织;然后,选择另 10 例健康供体和 20 例 AAD 患者的病理切片,通过免疫组织化学法验证蛋白质组学结果。
通过蛋白质组学分析鉴定了 809 种蛋白质,筛选出 132 种差异丰度蛋白(DAP),其中 100 种蛋白明显下调,32 种蛋白上调。在 100 种下调蛋白中,选择 2 种具有已知功能的蛋白,整合素α 3(ITGA-3)和 ITGA-5,作为与 AAD 发病机制相关的靶蛋白。通过免疫组织化学法验证了 2 个靶 DAP,结果表明 AAD 患者的 ITGA-3 和 ITGA-5 的积分光密度(IOD)明显低于健康供体,与蛋白质组学结果一致(<0.001)。
ITGA-3 和 ITGA-5 代表 AAD 发病机制的新型生物标志物,可能成为未来的治疗靶点。