• IBD;
  • colitis;
  • VEGF;
  • inflammation;
  • angiogenesis;
  • T cell



Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC), two widespread diseases of unknown, multifactorial etiology. Colitis pathology involves a pathological angiogenic response where increases in vascular density participate in colitis histopathology. Vascular endothelial growth factor-A (VEGF-A) is a potent angiogenesis stimulator known to be involved in pathological angiogenesis in several diseases including colitis. However, the pathogenic importance of specific VEGF-A isoforms during T-cell-mediated experimental colitis remains largely unknown.


The CD4+CD45RBhigh T-cell transfer model of experimental colitis was used for these studies. The VEGF lac-Z transgenic reporter mouse was used to examine specific cellular sources of VEGF-A production. The VEGF164 aptamer (Macugen), adenoviral VEGF164, and the VEGF Trap were used to evaluate pathological importance.


VEGF lac-Z reporter mice experiments showed that both infiltrating T cells and local tissue cells produce VEGF-A in the colon during disease. Inhibition of VEGF164 using a highly selective RNA aptamer significantly attenuated CD4+CD45RBhigh T-cell-dependent experimental colitis by reducing pathological angiogenesis and inflammatory pathology. Conversely, broad-spectrum VEGF inhibition with VEGF Trap did not attenuate disease, nor did adenoviral VEGF164 overexpression significantly alter colitis pathology.


VEGF164 is actively produced by multiple cell types during T-cell-mediated colitis. Importantly, specific inhibition of the VEGF164 isoform during T-cell-mediated colitis dose-dependently attenuated disease progression, while broad-scale inhibition of all VEGF-A isoforms was not therapeutically beneficial. (Inflamm Bowel Dis 2010)