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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-α-NFκB pathway.
MedLine Citation:
PMID:  22331014     Owner:  NLM     Status:  Publisher    
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-α in EoE samples compared to control. Further, there were higher nuclear levels of p50 and p65 subunits of NFκB and lower cellular levels of the inhibitor of NFκB, IκB-α, 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-α-NF-κB pathway, at least partially, played a role in mediating and triggering the observed inflammatory response-induced angiogenesis.
Rabindranath Persad; Hien Q Huynh; Li Hao; Jacqueline R Ha; Consolato Sergi; Rahul Srivastava; Sujata Persad
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-10
Journal Detail:
Title:  Journal of pediatric gastroenterology and nutrition     Volume:  -     ISSN:  1536-4801     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8211545     Medline TA:  J Pediatr Gastroenterol Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Department of Paediatrics, University of Alberta, Edmonton, Alberta, Canada †Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada. 1Co-first authors.
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