Human plasma LC-MSMS - Altered plasma proteins released from platelets and endothelial cells are associated with human patent ductus arteriosus

Patent ductus arteriosus (PDA) 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 closure-related human plasma proteins are unknown. Here we for the first time demonstrate six key differential plasma proteins in the human PDA patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. We found that permanent closure might be regulated by the proteins related to platelet activation and coagulation cascades, complement mannan-binding-lectin, and other systemic signaling pathways. Our findings indicate that the differential proteins involved in these pathways may play key roles in the non-closure of the ductus arteriosus and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of PDA.

动脉导管未闭（Patent ductus arteriosus, PDA）是第三大常见先天性心脏病，由出生后动脉导管持续开放引发。动脉导管闭合过程涉及受多种因素调控的功能与结构重塑，目前尚未明确与该闭合过程相关的人类血浆蛋白。本研究首次借助蛋白质组学技术（proteomic technology），在人类PDA患者中鉴定出6种关键差异血浆蛋白，并构建模型阐释动脉导管的收缩与闭合机制。研究发现，动脉导管的永久性闭合可能受血小板活化、凝血级联反应、补体甘露糖结合凝集素及其他全身信号通路相关蛋白的调控。本研究结果表明，参与上述通路的差异蛋白可能在动脉导管未闭的发生中发挥核心作用，并有潜力开发为临床诊断生物标志物。上述所有研究发现可为阐明PDA的病因与发病机制提供重要理论基础。