title: The finest branches of the biliary tree might induce biliary vascularization necessary for biliary regeneration.
abstract: OBJECTIVE
  The finer branches of the biliary tree play an important role in biliary regeneration. They are consistently escorted by microvessels. Defects in the vascularization of these structures could impair bile duct regeneration. Therefore, we investigated the pattern of the escorting microvessels during the development of bile duct loss in the human liver, using chronic rejection as a model.
  
  
  METHODS
  The number of interlobular bile ducts, bile ductules and extraportal biliary cells with and without escorting microvessels and the expression of VEGF-A were studied in follow-up biopsies of 12 patients with chronic rejection and 16 control patients with acute rejection without progression to chronic rejection.
  
  
  RESULTS
  The controls showed a proliferation of bile ductules at 1-week and 1-month. Proliferation of bile ductules without microvessels preceded proliferation of bile ductules with microvessels. Proliferation of the microvascular compartment followed biliary proliferation. This sequence of events was not observed in the chronic rejection group, in which all biliary structures decreased in time. VEGF-A expression was increased at 1-week and 1-month in both groups.
  
  
  CONCLUSIONS
  An immediate proliferative response of the finer branches of the biliary tree followed by proliferation of the microvascular compartment after biliary injury seems to be a prerequisite for bile duct regeneration.
authors.affiliation: Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands. m.c.van.den.heuvel@path.umcg.nl
authors.forename: Marius C
authors.initials: MC
authors.lastname: van den Heuvel
authors.forename: Annette S H
authors.initials: AS
authors.lastname: Gouw
authors.forename: Marcel
authors.initials: M
authors.lastname: Boot
authors.forename: Maarten J H
authors.initials: MJ
authors.lastname: Slooff
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
authors.forename: Koert P
authors.initials: KP
authors.lastname: de Jong
mesh_terms: D000208:Acute Disease; D017734:Bile Ducts, Extrahepatic / Q000098:blood supply* / Q000473:pathology / Q000502:physiology*; D001706:Biopsy; D002196:Capillaries / Q000473:pathology / Q000502:physiology; D002908:Chronic Disease; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D016031:Liver Transplantation; D018919:Neovascularization, Physiologic; D012038:Regeneration / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A