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059 A VEGF-MIMETIC ENHANCES GASTRIC ULCER HEALING IN MICE GK Dudar, GR Martin, L D'Andrea, C Pedone, JL Wallace Angiogenesis, the process of new blood vessel formation from pre-existing vessels, is crucial to all types of wound healing. The primary promoter of angiogenesis is VEGF (vascular endothelial growth factor). Platelets accumulate at sites of injury, where they can release VEGF upon activation. Previous studies from our laboratory indicate that platelets accelerate gastric ulcer healing in a VEGF-dependent manner (Br J Pharm 2006; 148: 274-278). We hypothesized that a VEGF mimetic would enhance gastric ulcer healing.
University of Calgary, Calgary, Alberta; University of Napoli Federico II, Napoli, Italy
Gastric ulcers were induced in C57BL6J mice by serosal application of acetic acid. The VEGF mimetic (100 ng/kg) or vehicle were administered i.p. twice-daily, beginning 3 days after ulcer induction. Ulcer areas were assessed on days 5, 7, and 10 after ulcer induction. In a second experiment, the effects of lower doses of the VEGF mimetic (25 ng/kg or 50 ng/kg) were tested. Ulcer areas were assessed 7 days after ulcer induction.
The average ulcer area at day 3 was 18.5 ± 0.6 mm2. In vehicle-treated mice, this decreased progressively: 15 ± 1 at day 5, 12.9 ± 1.2 at day 7 and 6.5 ± 0.5 at day 10. Treatment with the VEGF mimetic (100 ng/kg) accelerated healing: 11.2 ± 0.5 at day 5, 7.9 ± 0.9 at day 7 and 4.7 ± 0.2 at day 10. A dose of 50 ng/kg of the VEGF mimetic also accelerated ulcer healing, but at 25 ng/kg the VEGF mimetic had no significant effect.
Treatment with a VEGF mimetic accelerated gastric ulcer healing. VEGF mimetics may offer therapeutic promise for the treatment of gastric ulcers, as well as for the treatment of other types of wound. Ongoing studies are focused on the effects of the VEGF-mimetic on angiogenesis in the mouse gastric ulcer model.
Supported by a grant from the CIHR and by a CAG-CIHR-AstraZeneca Fellowship (to GRM)