| Absence of placental growth factor blocks dextran sodium sulfate-induced colonic mucosal angiogenesis, increases mucosal hypoxia and aggravates acute colonic injury. | |
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MedLine Citation:
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PMID: 20142801 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiogenesis has recently been described as a component of inflammatory bowel disease. Placental growth factor (PlGF), a vascular endothelial growth factor (VEGF) homologue, establishes its angiogenic capacity under pathophysiological conditions. We investigated the function of PlGF in experimental models of acute colitis. Acute colonic damage was induced in PlGF knock-out ((-/-)) mice and PlGF wild-type ((+/+)) mice by dextran sodium sulfate (DSS) and trinitrobenzenesulfonic acid (TNBS). The concentrations of PlGF and VEGF were measured in distal colonic lysates using an enzyme-linked immunosorbent assay. Colonic injury was evaluated by assessing colon length, colonocyte apoptosis (by terminal dUTP nick-end labeling), colonic cytokine production and histological score. Infiltration of polymorphonuclear cells was determined by assaying myeloperoxidase (MPO) activity. In a separate experiment, recombinant PlGF was administered to PlGF(-/-) mice by adenoviral transfer before DSS administration. Mucosal vascularization was quantified by computerized morphometric analysis of CD31-stained distal colonic sections. Colonic mucosal hypoxia was visualized by pimonidazole staining. Both VEGF and PlGF were upregulated during acute colitis. In addition, compared with PlGF(+/+) controls, PlGF(-/-) mice showed a significant increase in weight loss and colonic shortening during both DSS and TNBS colitis. This correlated with enhanced colonocyte apoptosis, elevated colonic cytokine levels and increased histological damage score, but not with enhanced inflammatory cell infiltration (MPO activity). The increased morbidity of PlGF(-/-) mice during DSS colitis was preventable by adenovirus (Ad)-mediated overexpression of PlGF. After the administration of DSS, strongly reduced mucosal angiogenesis was observed in PlGF(-/-) mice compared with PlGF(+/+) mice. This was associated with an early increase in intestinal epithelial pimonidazole accumulation in PlGF(-/-) mice, suggesting a function of enhanced epithelial hypoxia in the observed differences between the two groups. In summary, our data show that the absence of PlGF strongly inhibits mucosal intestinal angiogenesis in acute colitis, which is associated with an early increase in intestinal epithelial hypoxia and aggravation of the course of the disease. |
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Authors:
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Pieter Hindryckx; Anouk Waeytens; Debby Laukens; Harald Peeters; Jacques Van Huysse; Liesbeth Ferdinande; Peter Carmeliet; Martine De Vos |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-08 |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: 90 ISSN: 1530-0307 ISO Abbreviation: Lab. Invest. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-30 Completed Date: 2010-05-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: United States |
Other Details:
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Languages: eng Pagination: 566-76 Citation Subset: IM |
Affiliation:
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Department of Gastroenterology, Ghent University, De Pintelaan 185, Gent, Belgium. pieter.hindryckx@ugent.be |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / physiopathology Colitis, Ulcerative / pathology, physiopathology* Disease Models, Animal Mice Mice, Knockout Neovascularization, Pathologic / physiopathology* Pregnancy Proteins / physiology* Vascular Endothelial Growth Factor A / physiology |
| Chemical | |
Reg. No./Substance:
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0/Pregnancy Proteins; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; 144589-93-5/placenta growth factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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