title: Differential angiogenic regulation of experimental colitis.
abstract: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract with unknown multifactorial etiology that, among other things, result in alteration and dysfunction of the intestinal microvasculature. Clinical observations of increased colon microvascular density during IBD have been made. However, there have been no reports investigating the physiological or pathological importance of angiogenic stimulation during the development of intestinal inflammation. Here we report that the dextran sodium sulfate and CD4+CD45RBhigh T-cell transfer models of colitis stimulate angiogenesis that results in increased blood vessel density concomitant with increased histopathology, suggesting that the neovasculature contributes to tissue damage during colitis. We also show that leukocyte infiltration is an obligatory requirement for the stimulation of angiogenesis. The angiogenic response during experimental colitis was differentially regulated in that the production of various angiogenic mediators was diverse between the two models with only a small group of molecules being similarly controlled. Importantly, treatment with the anti-angiogenic agent thalidomide or ATN-161 significantly reduced angiogenic activity and associated tissue histopathology during experimental colitis. Our findings identify a direct pathological link between angiogenesis and the development of experimental colitis, representing a novel therapeutic target for IBD.
authors.affiliation: Department of Pathology, LSU Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Chidlow
authors.forename: Will
authors.initials: W
authors.lastname: Langston
authors.forename: James J M
authors.initials: JJ
authors.lastname: Greer
authors.forename: Dmitry
authors.initials: D
authors.lastname: Ostanin
authors.forename: Maisoun
authors.initials: M
authors.lastname: Abdelbaqi
authors.forename: Jeffery
authors.initials: J
authors.lastname: Houghton
authors.forename: Annamalai
authors.initials: A
authors.lastname: Senthilkumar
authors.forename: Deepti
authors.initials: D
authors.lastname: Shukla
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mazar
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Grisham
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000098:blood supply* / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000209:etiology*; D020556:Neutrophil Infiltration; D013792:Thalidomide / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide