title: Mouse strain influences angiogenic response to dextran sodium sulfate-induced colitis.
abstract: BACKGROUND
  Angiogenesis is a known pathologic factor in chronic inflammatory diseases. Regarding the murine dextran sodium sulfate (DSS) colitis model, different mouse strains produce variable clinical and inflammatory responses. We hypothesize that DSS colitis applied to diverse mouse strains will similarly elevate colonic microvessel density in parallel with inflammation, but will do so with different angiogenic profiles.
  
  
  METHODS
  We induced DSS colitis in 129S2/SvPas, BALB/c, and C57BL/6 mice, then performed histologic and molecular analysis at day 7 to evaluate colonic inflammation and angiogenesis.
  
  
  RESULTS
  Inflammation and microvessel density were similarly increased in DSS groups. The C57BL/6 cohort mounted a more severe colitis with 25% weight loss and greater colonic ulceration. Gene expression of angiogenic factors at baseline and in colitis groups were widely variable among strains. BALB/c mice exhibited higher angiogenic gene expression in control and DSS groups compared with other strains, specifically platelet-derived growth factor, angiopoietin-1, angiopoietin-1 (Ang-2), vascular endothelial growth factor receptor, and PDGF receptor. When evaluating the effect of DSS relative to controls, BALB/c mice were not significantly affected. 129S2/SvPas mice exhibited broad suppression of growth factors, significantly platelet-derived growth factor, Ang-2, and PDGF receptor. In contrast, C57BL/6 mice displayed increased gene expression, especially for angiopoietin-1 and Ang-2.
  
  
  CONCLUSIONS
  Genetic heterogeneity influences the angiogenic profile elicited by DSS colitis. We demonstrate that within a model of murine colitis, mouse strain significantly affects inflammation-associated angiogenesis. These results may impact strain selection when using a colitis model focusing on inflammation and angiogenesis. Future studies to further define the angiogenesis pathway and potentially alter the disease course with targeted antiangiogenics are warranted.
authors.affiliation: Colorectal Center for Children, Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center.
authors.forename: Jennifer Leslie
authors.initials: JL
authors.lastname: Knod
authors.affiliation: Colorectal Center for Children, Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center.
authors.forename: Kelly
authors.initials: K
authors.lastname: Crawford
authors.affiliation: Colorectal Center for Children, Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center.
authors.forename: Mary
authors.initials: M
authors.lastname: Dusing
authors.affiliation: Colorectal Center for Children, Division of Pediatric General & Thoracic Surgery, Cincinnati Children's Hospital Medical Center. Electronic address: Jason.Frischer@cchmc.org.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Frischer
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000503:physiopathology; D003106:Colon / Q000098:blood supply; D016264:Dextran Sulfate / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000098:blood supply; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016264:Dextran Sulfate; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Angiogenesis; Colitis; Dextran sodium sulfate; Murine model