ISMICS Home  |  Past & Future Meetings
Countdown to ISMICS : -33 Days  
International Society For Minimally Invasive Cardiothoracic Surgery

Back to 2020 Display ePosters


Itraq Proteomics Reveals Map2k1 As The Foundation Of Human Ductus Arteriosus Closure
Yingying Xiao1, Lincai Ye2, Minghui Li3, Xiuxia Ye4, Xinxin Yan5, Xu Liu5, Huiwen Chen5, Chuan Jiang2, Haibo Zhang6, Jinfen Liu2, Yanlin Wang7, Haifa Hong6.
1Shanghai Jiaotong University of Medicine, Shanghai, China, 2Institute of Pediatric Translational Medicine,Shanghai Children's Medical Center,Shanghai Jiaotong University of Medicine, Shanghai, China, 3Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China, 4Neonatology department, Shanghai Children's Medical Center,Shanghai Jiaotong University of Medicine, Shanghai, China, 5Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center,Shanghai Jiaotong University of Medicine, Shanghai, China, 6Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China, 7International Peace Maternity And Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

BACKGROUND Effective control of the closure of the ductus arteriosus (DA) is necessary for thetreatment of ductus arteriosus dependent congenital heart disease(DACHD). Current Prostaglandins-based management is limited in severe complications. In this study,we verified the importance of MAP2K1 and explored the underling mechanism of MAP2K1 regulating DA patency.METHODS We compared 20 constricted and 20 patent human DAs excised from infants with DACHD,using isobaric tags for relative and absolute quantitation based quantitative proteomics(iTRAQ).Prenatal and postnatal mice injected with or without PD0325901( MAP2K1 inhibitor) were sacrificed to visualize the patency of DA by ink injection. Ductus arteriosus smooth muscle cells (DASMCs) isolated from human DA tissues and knocked out MAP2K1 were used to test for :1)their intracellular calcium by flow cytometery;2) migration ability by hyaluronic acid secretion and transwell experiments; and 3) proliferative ability by EdU staining and CCK8 experiments;RESULTS We found 452 differentially expressed proteins via iTRAQ, of which Gene Ontology(GO) and KEGG Network Analysis showed MAP2K1(Uniprot_accession:Q02750) is the most important. In vivo study, MAP2K1 inhibition by PD0325901 is sufficient to keep mouse DA patent. In vitro study, knocking out MAP2K1 alone can only affect the functional closure of the DA while knocking out MAP2K1 homologous analogue MAP2K2 alone can only affect the anatomic closure of the DA.CONCLUSIONS We concluded that MAP2K1 is the cornerstone of the DA closure process and modification of MAP2K1 related pathway may hold therapeutic promise to keep DA patency.


Back to 2020 Display ePosters
Poland
Poland
Poland
Poland
By using this site, you agree to our updated Privacy Policy.  Got it