Efficacy of vascular endothelial growth factor in the treatment of experimental gastric injury.
OBJECTIVE
Studies indicate that angiogenesis is important in tissue healing. However, the role of vascular endothelial growth factor (VEGF) in tissue healing has not been established. The aim of the study is to determine whether VEGF has a gastroprotective role in experimental gastric injury.


METHODS
Acute gastric injury was induced in Sprague-Dawley rats by intragastric administration of 100% ethanol. Expression of gastric VEGF was determined in tissue homogenates by enzyme-linked immunosorbent assay and in paraffin-embedded sections by immunohistochemistry. The effect of systemic administration of anti-VEGF antibodies and recombinant VEGF on injury severity was assessed macroscopically and microscopically.


RESULTS
Gastric VEGF concentrations peaked at 6 h and again 3 days after acute injury. The presence of VEGF was demonstrated in epithelial cells and in mononuclear cells. Blocking endogenous VEGF effects with anti-VEGF antibodies exacerbated mucosal injury. Administration of recombinant VEGF after the onset of injury reduced the severity of mucosal injury, irrespective of the timing of initial treatment with VEGF. Immunohistochemical detection of vascular endothelial cells revealed that the VEGF-induced mucosal repair is closely related to the degree of angiogenesis.


CONCLUSIONS
The results provide strong evidence for the role of VEGF in the repair of tissue damage induced by ethanol. The results also show how VEGF may be used in a clinical setting to treat some acute gastric lesions.
Matsui
Yutaka
Y
Second Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Mitsuyama
Keiichi
K
Tomiyasu
Nobuo
N
Toyonaga
Atsushi
A
Sata
Michio
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000431:Ethanol