Altered plasma proteins released from platelets and endothelial cells are associated with human patent ductus arteriosus
Altered plasma proteins released from platelets and endothelial cells are associated with human patent ductus arteriosus
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DOI：
10.1002/jcp.27433
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发表时间：
2019-05-01
影响因子：
5.6
通讯作者：
He, Guo-Wei
中科院分区：
文献类型：
--
作者：
Hou, Hai-Tao;Xi-Zhang;He, Guo-Wei
动脉导管未闭是第三大常见的先天性心脏病，是由于出生后导管持续通畅所致。动脉粥样硬化闭塞涉及功能和结构重建，受多种因素控制。与PDA闭合相关的血浆蛋白水平变化尚不清楚。在这里，我们第一次展示了六个关键的差异血浆蛋白在人类动脉导管未闭患者使用蛋白质组学技术，并提出了一个模型来说明动脉导管的收缩和关闭。差异表达的蛋白质进行了分析，通过使用同量异位素标签的相对和绝对定量，并验证了酶联免疫吸附试验在新的样品。蛋白质组学数据已通过PRIDE合作伙伴存储库存入ProteomeXchange Consortium，数据集标识符为PXD 008568。我们在PDA患者血浆中发现74种上调和98种下调蛋白。五种蛋白质（血小板因子4、纤维蛋白原、血管性血友病因子、胶原蛋白和甘露糖结合凝集素相关丝氨酸蛋白酶-2）减少和一种蛋白质（纤连蛋白）增加可能增加动脉导管未闭的风险。这些蛋白质与血小板活化和凝血级联反应、补体甘露聚糖结合凝集素和其他系统性信号通路密切相关。我们的研究结果首次表明，参与不同途径的差异蛋白可能在人类动脉导管未闭合中发挥关键作用，并可能发展为诊断的生物标志物。这些结果为进一步认识动脉导管未闭的病因和发病机制提供了依据。
Patent ductus arteriosus is the third most common congenital heart disease and resulted from the persistence of ductal patency after birth. Ductus arteriosus closure involves functional and structural remodeling, controlled by many factors. The changes in plasma protein levels associated with PDA closure are not known. Here we for the first time demonstrate six key differential plasma proteins in human patent ductus arteriosus patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. Differentially expressed proteins were analyzed by using isobaric tags for relative and absolute quantification and validated by enzyme-linked immunosorbent assay in new samples. The proteomic data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD008568. We found 74 upregulated and 98 downregulated proteins in the plasma of patients with PDA. Five decreased proteins (platelet factor 4, fibrinogen, von Willebrand factor, collagen, and mannose binding lectin-associated serine protease-2) and one increased protein (fibronectin) may increase the risk of patent ductus arteriosus. Those proteins are closely related to platelet activation and coagulation cascades, complement mannan-binding-lectin, and other systemic signaling pathways. Our findings for the first time indicate that the differential proteins involved in different pathways may play key roles in the nonclosure of the ductus arteriosus in humans and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of patent ductus arteriosus.