title: VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164b therapy.
abstract: BACKGROUND
  Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165(b) (VEGF164(b) in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia.
  
  
  RESULTS
  The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164(b) expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164(b), which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164(b) expression.
  
  
  CONCLUSIONS
  This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164(b) expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC.
authors.affiliation: Gene Therapy Program, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA. jmathi@lsuhsc.edu.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Cromer
authors.forename: Chaitanya V
authors.initials: CV
authors.lastname: Ganta
authors.forename: Mihir
authors.initials: M
authors.lastname: Patel
authors.forename: James
authors.initials: J
authors.lastname: Traylor
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander
authors.forename: J Michael
authors.initials: JM
authors.lastname: Mathis
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D002449:Cell Aggregation / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D018450:Disease Progression; D057809:HEK293 Cells; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D042601:Lymphatic Vessels / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020033:Protein Isoforms; D014302:Trinitrobenzenesulfonic Acid; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020011:Protective Agents; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate
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