Updated publication reference for PubMed record(s): 30480800. 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.