Submitted on May 5, 2008
Revised on June 17, 2008
Accepted on June 20, 2008
A Vascular Endothelial Growth Factor Mimetic Accelerates Gastric Ulcer Healing in an iNOS-Dependent Manner
Genevieve K Dudar1, Luca D D'Andrea2, Rossella Di Stasi2, Carlo Pedone2, and John L. Wallace1*
1 University of Calgary
2 Consiglio Nazionale delle Ricerche
* To whom correspondence should be addressed. E-mail: wallacej{at}ucalgary.ca.
Angiogenesis is crucial to all types of wound healing, including gastric ulcer healing. The most potent promoter of angiogenesis is VEGF (vascular endothelial growth factor). We hypothesized that a 15-amino acid peptide designed to mimic the angiogenic action of VEGF would accelerate gastric ulcer healing. Gastric ulcers were induced in mice by serosal application of acetic acid. Treatment with the VEGF mimetic accelerated gastric ulcer healing when administered orally or intraperitoneally, at a dose of 50 ng/kg or greater. Such healing was not observed when the reverse sequence pentadecapeptide or the full-length VEGF protein was administered. Contrary to our hypothesis, the VEGF mimetic did not significantly increase angiogenesis in the ulcerated stomach. The enhancement of ulcer healing by the VEGF mimetic occurred independently of cyclooxygenase-2 activity, but was blocked by inhibitors of inducible nitric oxide synthase. These results demonstrate that a VEGF mimetic is a potent stimulus for gastric ulcer healing, even when given orally. The effects of the mimetic were independent of stimulatory effects on angiogenesis and cyclooxygenase-2 activity, but were dependent on iNOS-derived nitric oxide production.
