title: Increased angiogenesis and permeability in the mesenteric microvasculature of rats with cirrhosis and portal hypertension: an in vivo study.
abstract: BACKGROUND
  In vivo evidence for angiogenesis in the splanchnic vasodilation in portal hypertension (PHT) and cirrhosis is lacking. Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) are mediators of angiogenesis. The present study visualises in vivo structural changes (angiogenesis and vascular hyperpermeability) and examines the presence of VEGF and eNOS in the mesenteric microvasculature of animal models of PHT with and without cirrhosis.
  
  
  METHODS
  Portal hypertension was induced by partial portal vein ligation (PPVL) and cirrhosis was induced by common bile duct ligation (CBDL) in rats. The mesenteric microcirculation was examined by intravital microscopy. Expression of VEGF, eNOS and CD31 in mesenteric tissue were studied by immunohistochemistry.
  
  
  RESULTS
  An increased mesenteric angiogenesis was observed in PPVL and CBDL rats compared with Sham-operated and control rats, as shown by intravital microscopy and CD 31 staining. VEGF and eNOS expression was higher in CBDL and PPVL rats compared with control groups and correlated positively with vascular density. Macromolecular leakage was increased in cirrhotic rats compared with control and PPVL rats.
  
  
  CONCLUSIONS
  Our study provides in vivo evidence of an increased angiogenesis in the mesenteric microvasculature of animal models of PHT and cirrhosis. Increased VEGF and eNOS expression in the mesentery of PPVL and CBDL rats may suggest their contribution. Microvascular permeability in the mesenteric vessels was only increased in cirrhotic rats.
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium. anja.geerts@UGent.be
authors.forename: Anja M
authors.initials: AM
authors.lastname: Geerts
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
authors.forename: Eline
authors.initials: E
authors.lastname: Vanheule
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.forename: Siska
authors.initials: S
authors.lastname: Mortier
authors.forename: Kin-Jip
authors.initials: KJ
authors.lastname: Cheung
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.forename: Norbert
authors.initials: N
authors.lastname: Lameire
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colle
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D003135:Common Bile Duct / Q000473:pathology; D004195:Disease Models, Animal; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000378:metabolism; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D011169:Portal Vein / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III