title: Angiogenesis and Vascular Endothelial Growth Factor-A Expression Associated with Inflammation in Pediatric Crohn's Disease.
abstract: OBJECTIVE
  Angiogenesis is a component of chronic inflammatory diseases including inflammatory bowel disease. Some studies describe increased angiogenesis associated with acute disease in adult Crohn's disease and ulcerative colitis, while animal models aid investigations of mechanism and pathophysiology of angiogenesis. We aim to explore the role of angiogenesis and its pathways in pediatric Crohn's disease.
  
  
  METHODS
  Surgical specimens were obtained from pediatric Crohn's disease (both inflamed and non-inflamed regions of ileum) and control patients. Samples were examined for inflammation, microvessel density, and molecular expression of vascular endothelial growth factor-A, platelet-derived growth factor-β, angiopoietin-1, and angiopoietin-2.
  
  
  RESULTS
  Angiogenesis and inflammation were increased in parallel in Crohn's disease compared to controls. We also discovered increased angiogenesis in Crohn's disease tissue that was relatively free of inflammatory disease. Vascular endothelial growth factor-A gene expression (P = 0.034) was elevated in Crohn's disease over controls, while gene expression of platelet-derived growth factor-β (P = 0.069), angiopoietin-1 (P = 0.206), and angiopoietin-2 (P = 0.082) was not significantly elevated.
  
  
  CONCLUSIONS
  We confirm that inflammation-associated angiogenesis is upregulated in pediatric Crohn's disease. This population also exhibits elevated mucosal angiogenesis at the surgical margin with limited inflammation. This suggests that angiogenesis is an additional pathologic characteristic to potentially identify normal mucosa and margins of surgical resection that are uninvolved with disease and, furthermore, may have implications for monitoring complete disease remission. We further identify the vascular endothelial growth factor-A pathway involvement in the disease process, which may serve as a future molecular target for anti-angiogenic therapy in inflammatory bowel disease.
authors.affiliation: Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: J Leslie
authors.identifier: http://orcid.org/0000-0002-9627-4334
authors.initials: JL
authors.lastname: Knod
authors.affiliation: Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Crawford
authors.affiliation: Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Dusing
authors.affiliation: Division of Pediatric Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.affiliation: Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Artur
authors.initials: A
authors.lastname: Chernoguz
authors.affiliation: Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Jason.Frischer@cchmc.org.|Director, Colorectal Center for Children, Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnett Avenue, MLC-2023, Cincinnati, OH, 45229, USA. Jason.Frischer@cchmc.org.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Frischer
mesh_terms: D000367:Age Factors; D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009389:Neovascularization, Pathologic; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D010982:Platelet-Derived Growth Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Crohn’s disease; Pediatric; VEGF-A