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Angiogenic remodeling in pediatric eosinophilic esophagitis is associated with increased levels of VEGFA, angiogenin, IL-8 and activation of the TNF-alpha-NFkappaB pathway.

Authors: Persad, R  Huynh, HQ  Hao, L  Ha, JR  Sergi, C  Srivastava, R  Persad, S 
Citation: Persad R, etal., J Pediatr Gastroenterol Nutr. 2012 Feb 10.
Pubmed: (View Article at PubMed) PMID:22331014
DOI: Full-text: DOI:10.1097/MPG.0b013e31824b6391

ABSTRACT: Eosinophilic Esophagitis (EoE) is a clinicopathologic diagnosis characterized by inflammation and infiltration of eosinophils at the esophageal mucosa. The underlying etiology of EoE remains elusive. Inflammatory diseases, such as asthma, are associated with structural remodeling of the airways, which includes angiogenesis. We compared the angiogenic profile of the esophageal mucosa of pediatric patients presenting with EoE relative to control. In addition, we investigated putative mechanism(s) that may be involved in the pathogenesis of the inflammatory angiogenic response observed in EoE. METHODS & RESULTS:: Endoscopically obtained biopsy samples from 18 EoE and 18 control pediatric patients were analyzed for angiogenic markers (CD-31, vWF, VCAM-1) and tissue levels of angiogenic factors (VEGFA, VEGF R2, angiogenin and IL-8). Samples from EoE patients exhibited higher levels of vWF, CD31 and VCAM-1 suggestive of neovascularization and an activated endothelium. Moreover, EoE biopsies showed greater levels of the angiogenesis promoters, VEGFA, angiogenin and IL-8. Interestingly, there were greater cellular levels of TNF-alpha in EoE samples compared to control. Further, there were higher nuclear levels of p50 and p65 subunits of NFkappaB and lower cellular levels of the inhibitor of NFkappaB, IkappaB-alpha, in EoE samples compared to control. CONCLUSIONS:: We demonstrate increased angiogenesis in the esophageal mucosa of pediatric patients with EoE. The data also provided evidence that the angiogenic factors VEGFA, angiogenin and IL-8 were prominently involved in promoting angiogenic remodeling. Furthermore, activation of the TNF-alpha-NF-kappaB pathway, at least partially, played a role in mediating and triggering the observed inflammatory response-induced angiogenesis.


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CRRD Object Information
CRRD ID: 6771318
Created: 2012-07-25
Species: All species
Last Modified: 2012-07-25
Status: ACTIVE


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