Differential angiogenic regulation of experimental colitis.
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.
Chidlow
John H
JH
Department of Pathology, LSU Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA.
Langston
Will
W
Greer
James J M
JJ
Ostanin
Dmitry
D
Abdelbaqi
Maisoun
M
Houghton
Jeffery
J
Senthilkumar
Annamalai
A
Shukla
Deepti
D
Mazar
Andrew P
AP
Grisham
Matthew B
MB
Kevil
Christopher G
CG
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*
D020533:Angiogenesis Inhibitors; D013792:Thalidomide