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Hypoxic‐ischemic gene expression profile in the isolated variant of biliary atresia
Author(s) -
Fratta Leila Xavier Sinigaglia,
Hoss Giovana Regina Weber,
Longo Larisse,
UribeCruz Carolina,
Silveira Themis Reverbel,
Vieira Sandra Maria Gonçalves,
Kieling Carlos Oscar,
Santos Jorge Luiz
Publication year - 2015
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.297
Subject(s) - biliary atresia , medicine , cardiology , biology , liver transplantation , transplantation
Abstract Background Biliary atresia (BA) includes a sclerosing cholangiopathy whose nature is not fully deciphered. Aiming to evaluate the role of an arteriopathy as an etiologic factor in BA, we investigated hypoxia and the correlated angiogenic response in livers from affected patients. Methods Gene expression of the molecular axis: hypoxia‐inducible factor ( HIF ) 1a , HIF2a and vascular endothelial growth factor A ( VEGFA )/ VEGFR1 , VEGFR2 . Liver biopsy specimens collected at exploratory laparotomy of age‐matched patients with isolated, cytomegalovirus IgM‐negative BA ( n = 32) and intrahepatic cholestasis (IHC, n = 9) were evaluated. Results We observed higher HIF1a and HIF2a expression in BA than in IHC. Paradoxically, VEGFR2 , the main target of VEGFA‐induced angiogenesis, was underexpressed in BA, and VEGFA was decreased in most BA patients. Patients with the highest expression of HIF s and the lowest VEGFA and VEGFR2 were essentially the same, indicating hypoxia without the necessary angiogenesis. This group included most BA patients and, except for HIF2a , they were older and presented increased bilirubin serum levels. In the highest HIF2a /lowest VEGFR2 subsets, gene expression of the cytokeratin 19, marker of cholangiocyte phenotype, was decreased. Conclusion This study suggests that hypoxia‐ischemia is present in the livers of patients with BA, progresses over time and leads to a decreased cholangiocyte mass.