title: Hepatic microcirculation and cholangiocyte physiopathology.
abstract: BACKGROUND
  The peribiliary plexus (PBP) plays a fundamental role in supporting the functions of the biliary epithelium. After common bile duct ligation (BDL) progressive PBP proliferation is demonstrated. We have, recently, demonstrated that the biliary epithelium express Vascular Endothelial Growth Factor (VEGF), both subtype -A and -B and VEGF receptors. Taking in consideration the wide extension of PBP during BDL, aim of our study is to investigate the role of VEGF in stimulating angiogenesis and also in the modulation of epithelial cells proliferation.
  
  
  METHODS
  Experimental studies were performed by evaluating the effects of: a) endogenous VEGF neutralization by chronic administration of anti VEGF-C antibody on cholangiocyte proliferation in BDL rats and; b) the hepatic artery ligation (HAL) immediately after BDL followed by treatment (7 days) with a recombinant of VEGF-A (administered through IP implanted minipumps) on cholangiocyte proliferative activities.
  
  
  RESULTS
  Both administration of antiVEGF-C antibody and HAL decreases cholangiocyte proliferation. The decrease of cholangiocyte proliferation was associated with depressed VEGF-A protein expression. The administration of rVEGF-A to BDL, hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats.
  
  
  CONCLUSIONS
  These data suggest that VEGF-C modulates the proliferative activities of cholangiocytes in experimental cholestasis and that circulating factors (i.e., VEGF) in the blood supply of the intra-hepatic biliary epithelium, play an important role in the balance between cholangiocyte proliferation/loss.
authors.affiliation: Department of Anatomy, University of Rome La Sapienza, Rome, Italy. eugenio.guadio@uniroma1.it
authors.forename: E
authors.initials: E
authors.lastname: Gaudio
authors.forename: P
authors.initials: P
authors.lastname: Onori
authors.forename: A
authors.initials: A
authors.lastname: Franchitto
authors.forename: L
authors.initials: L
authors.lastname: Pannarale
authors.forename: G
authors.initials: G
authors.lastname: Alpini
authors.forename: D
authors.initials: D
authors.lastname: Alvaro
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001284:Atrophy / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001653:Bile Ducts, Intrahepatic / Q000098:blood supply* / Q000166:cytology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006499:Hepatic Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor