Increased angiogenesis and permeability in the mesenteric microvasculature of rats with cirrhosis and portal hypertension: an in vivo study.
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.
Geerts
Anja M
AM
Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium. anja.geerts@UGent.be
De Vriese
An S
AS
Vanheule
Eline
E
Van Vlierberghe
Hans
H
Mortier
Siska
S
Cheung
Kin-Jip
KJ
Demetter
Pieter
P
Lameire
Norbert
N
De Vos
Martine
M
Colle
Isabelle
I
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
D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III