| Role of placental growth factor in mesenteric neoangiogenesis in a mouse model of portal hypertension. | |
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MedLine Citation:
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PMID: 19751735 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-12 |
Journal Detail:
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Title: Gastroenterology Volume: 137 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-07 Completed Date: 2009-12-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 2112-24.e1-6 Citation Subset: AIM; IM |
Affiliation:
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Faculty of Medicine and Health Sciences, Department of Hepatology and Gastroenterology, Ghent University, Ghent, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenic Proteins
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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:
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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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