title: Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia.
abstract: BACKGROUND
  Biliary atresia (BA) is an infantile disorder characterized by progressive sclerosing cholangiopathy leading to biliary obstruction. First-line treatment of BA is hepatoportoenterostomy, the prognosis of which is related to age at surgery and to histological variables such as extent of fibrosis and ductular reaction. Hepatic arterial medial thickening (MT) suggests an arteriopathy in BA pathogenesis. We evaluated the expression of angiopoietin (ANGPT)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (TIE2) system in liver samples obtained from patients with BA, correlating it with MT, variables associated with disease severity, and postoperative prognosis.
  
  
  METHODS
  ANGPT1, ANGPT2, and TIE2 expression levels were assessed by quantitative PCR in liver samples obtained from BA patients (n = 23) at portoenterostomy and age-matched infants with intrahepatic cholestasis (IHC; n = 7). Histological variables were morphometrically assessed.
  
  
  RESULTS
  ANGPT1 and ANGPT2 were overexpressed in BA in comparison with IHC (P = 0.024 and P = 0.029, respectively). In BA, ANGPTs expression was positively correlated with MT (ANGPT1: rs = 0.59, P = 0.013; ANGPT2: rs = 0.52, P = 0.032), not with the variables associated with disease severity. TIE2 and ANGPTs expression levels were negatively correlated (ANGPT1: rs = -0.73, P < 0.001; ANGPT2: rs = -0.54, P = 0.007).
  
  
  CONCLUSIONS
  In BA, there is overexpression of both ANGPT1 and ANGPT2, which is correlated with MT but not with age at portoenterostomy or with the histological variables associated with disease severity at the time of procedure.
authors.affiliation: 1] Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil [2] Experimental Laboratory of Hepatology and Gastroenterology, Research Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Aline F
authors.initials: AF
authors.lastname: de Souza
authors.affiliation: 1] Laboratory of Pathology, Research Center of Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil [2] Department of Pathology, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.affiliation: 1] Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil [2] Experimental Laboratory of Hepatology and Gastroenterology, Research Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Themis R
authors.initials: TR
authors.lastname: da Silveira
authors.affiliation: Experimental Laboratory of Hepatology and Gastroenterology, Research Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Cleandra
authors.initials: C
authors.lastname: Gregório
authors.affiliation: Experimental Laboratory of Hepatology and Gastroenterology, Research Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Najara
authors.initials: N
authors.lastname: Reus
authors.affiliation: Gene Therapy Center, Research Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Uribe
authors.affiliation: 1] Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil [2] Gene Therapy Center, Research Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.affiliation: 1] Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil [2] Department of Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Rio Grande do Sul, Brazil.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: dos  Santos
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000502:physiology*; D042702:Angiopoietin-2 / Q000235:genetics / Q000502:physiology*; D001656:Biliary Atresia / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D015870:Gene Expression; D006499:Hepatic Artery / Q000473:pathology*; D006801:Humans; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2