Document Detail


Role of placental growth factor in mesenteric neoangiogenesis in a mouse model of portal hypertension.
MedLine Citation:
PMID:  19751735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Portal hypertension is responsible for the major complications associated with cirrhosis. Angiogenesis has been associated with the pathophysiology of portal hypertension. We investigated the role of placental growth factor (PlGF) and tested the effects of monoclonal antibodies against PlGF (alphaPlGF) in a mouse model of portal hypertension. METHODS: Using a mouse model of prehepatic portal hypertension, we measured PlGF levels in the mesenteric tissue at different time points. We used knockout mice and alphaPlGF to determine the role of PlGF in the splanchnic hyperdynamic system and portosystemic collateral formation, examining its effects before and after portal hypertension was induced. RESULTS: PlGF was significantly up-regulated in the mesenteric tissue of mice with portal hypertension. Compared with wild-type animals, the vascular density in the mesentery was reduced in PlGF knockout hypertensive mice, preventing collateral formation and attenuation of mesenteric artery flow without affecting portal pressure. In the prevention study, alphaPlGF showed similar findings as in the knockout study. In mice with portal hypertension, administration of alphaPlGF resulted in a 32% decrease in portal pressure, compared with mice given immunoglobulin G(1) (control). CONCLUSIONS: Pathologic angiogenesis in the mesenteric tissues of mice with portal hypertension is mediated by PlGF. Blocking PlGF could be an effective strategy for reducing collateral formation and lowering portal pressure; further research into the effects in cirrhosis is warranted.
Authors:
Christophe Van Steenkiste; Anja Geerts; Eline Vanheule; Hans Van Vlierberghe; Filip De Vos; Kim Olievier; Christophe Casteleyn; Debby Laukens; Martine De Vos; Jean-Marie Stassen; Peter Carmeliet; Isabelle Colle
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-12
Journal Detail:
Title:  Gastroenterology     Volume:  137     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2009-12-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2112-24.e1-6     Citation Subset:  AIM; IM    
Affiliation:
Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Angiogenic Proteins / metabolism
Animals
Antibodies, Monoclonal / pharmacology
Antihypertensive Agents / pharmacology
Collateral Circulation* / drug effects
Disease Models, Animal
Hypertension, Portal / drug therapy,  metabolism*,  physiopathology
Kinetics
Male
Mesentery / blood supply*,  metabolism*
Mice
Mice, Knockout
Microcirculation
Neovascularization, Pathologic / metabolism*,  physiopathology,  prevention & control
Portal Pressure
Pregnancy Proteins / deficiency,  genetics,  immunology,  metabolism*
Signal Transduction
Splanchnic Circulation* / drug effects
Up-Regulation
Chemical
Reg. No./Substance:
0/Angiogenic Proteins; 0/Antibodies, Monoclonal; 0/Antihypertensive Agents; 0/Pregnancy Proteins; 144589-93-5/placenta growth factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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