Platelets accelerate gastric ulcer healing through presentation of vascular endothelial growth factor.
1. Platelets contain an array of growth factors that can modulate healing processes, including both pro- (e.g., vascular endothelial growth factor (VEGF)) and antiangiogenic (e.g., endostatin) factors. Previous studies have shown that circulating platelets contribute significantly to gastric ulcer healing, acting as a delivery system for these growth factors to the site of injury. In this study, we examined the effects of orally administered human platelets on the healing of gastric ulcers in rats, and determined the contribution of VEGF and endostatin to healing in this model. 2. Twice-daily administration of human platelets significantly accelerated ulcer healing, but platelet-poor plasma (PPP), lysed platelets and serum failed to produce this effect. There was no correlation between ulcer healing and the levels of VEGF or endostatin in serum, PPP or platelet-rich plasma (PRP). 3. Accelerated ulcer healing could not be produced by oral administration of the angiogenic factors themselves, at concentrations matching those in PRP. 4. The accelerated healing induced by platelets could be reversed by immuno-neutralization of VEGF. In contrast, immuno-neutralization of endostatin did not affect PRP-induced ulcer healing. 5. These studies indicate that VEGF released from platelets accounts for the accelerated healing of gastric ulcers. However, as intact (rather than lysed) platelets were required for the accelerated healing, the presentation of VEGF by the platelet at the site of injury appears to be crucial for enhancement of the healing process.
Wallace
John L
JL
Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, Canada. wallacej@ucalgary.ca
Dicay
Michael
M
McKnight
Webb
W
Dudar
Genevieve K
GK
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000502:physiology*; D016503:Drug Delivery Systems; D043169:Endostatins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D017713:Platelet Transfusion; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
D043169:Endostatins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A