Differential angiogenic regulation of experimental colitis

John H. Chidlow, Will Langston, James J M Greer, Dmitry Ostanin, Maisoun Abdelbaqi, Jeffery Houghton, Annamalai Senthilkumar, Deepti Shukla, Andrew P. Mazar, Matthew B. Grisham, Christopher G. Kevil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2014-2030
Number of pages17
JournalAmerican Journal of Pathology
Volume169
Issue number6
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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