Mechanistic and pharmacologic role of placental growth factor in experimental ulcerative colitis in rats

Abstract

We demonstrated that vascular endothelial growth factor accelerated the healing of experimental duodenal ulcer but aggravated ulcerative colitis (UC), probably because of the differences in ulcer healing. Since placental growth factor (PlGF) enhances abnormal (“pathologic”) angiogenesis, we measured its expression and role in experimental UC. Groups of rats were given iodoacetamide (IA) to cause UC and they were euthanized at 0.5, 2, 6, 12, 24, 48, and 84 hr after IA. Additional groups of rats were given neutralizing anti‐PlGF antibody, IgG (50ug/rat, i.m.) or saline on 2nd and 5th days and euthanized 7th day after IA when the extent of UC was evaluated macroscopically and by microscopy. Mucosal scrapings of distal colon were obtained at autopsy. Expression of PlGF was measured by Western blotting.ResultsExpression of PlGF protein was enhanced at 2 hr, with further increases (+50–80%) until 7 days. Inhibition of PlGF significantly reduced the levels of colonic PlGF, i.e., 2‐ to 3‐folds compared to control. Colonic lesions were also decreased from 323.2±44.1 (controls) to 209.8±31.2 mm2 (anti‐PlGF) (p < 0.05).Conclusions1) The sustained increase in expression of PlGF in UC may indicate an abnormal (pathologic) angiogenesis occurring in the development of UC. 2) Inhibition of PlGF attenuated experimental UC development. 3) Thus, PlGF may play a pathogenic & therapeutic role in the development & healing of UC.(This work was supported by the Veterans Health Administration Merit Review Grants to Zs. Sandor and S. Szabo)