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VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis.

Authors: Scaldaferri, F  Vetrano, S  Sans, M  Arena, V  Straface, G  Stigliano, E  Repici, A  Sturm, A  Malesci, A  Panes, J  Yla-Herttuala, S  Fiocchi, C  Danese, S 
Citation: Scaldaferri F, etal., Gastroenterology. 2009 Feb;136(2):585-95.e5. Epub 2008 Oct 7.
Pubmed: (View Article at PubMed) PMID:19013462
DOI: Full-text: DOI:10.1053/j.gastro.2008.09.064

BACKGROUND & AIMS: Vascular endothelial growth factor A (VEGF-A) mediates angiogenesis and might also have a role in inflammation and immunity. We examined whether VEGF-A signaling has a role in inflammatory bowel disease (IBD). METHODS: Expression levels of VEGF-A, and its receptors VEGFR-1 and VEGFR-2, were examined in samples from patients with IBD and compared with those of controls. The capacity of VEGF-A to induce angiogenesis was tested in human intestinal microvascular endothelial cells using cell-migration and matrigel tubule-formation assays. Levels of vascular cellular adhesion molecule-1 and intercellular adhesion molecule were measured by flow cytometry to determine induction of inflammation; neutrophil adhesion was also assayed. Expression patterns were determined in tissues from mice with dextran sulfate sodium (DSS)-induced colitis; the effects of VEGF-A overexpression and blockade were assessed in these mice by adenoviral transfer of VEGF-A and soluble VEGFR-1. Intestinal angiogenesis was measured by quantitative CD31 staining and leukocyte adhesion in vivo by intravital microscopy. RESULTS: Levels of VEGF-A and VEGFR-2 increased in samples from patients with IBD and colitic mice. VEGF-A induced angiogenesis of human intestinal microvascular endothelial cells in vitro as well as an inflammatory phenotype and adherence of neutrophils to intestinal endothelium. Overexpression of VEGF-A in mice with DSS-induced colitis worsened their condition, whereas overexpression of soluble VEGFR-1 had the opposite effect. Furthermore, overexpression of VEGF-A increased mucosal angiogenesis and stimulated leukocyte adhesion in vivo. CONCLUSIONS: VEGF-A appears to be a novel mediator of IBD by promoting intestinal angiogenesis and inflammation. Agents that block VEGF-A signaling might reduce intestinal inflammation in patients with IBD.


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CRRD Object Information
CRRD ID: 5684406
Created: 2011-12-19
Species: All species
Last Modified: 2011-12-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.