Role of vascular endothelial growth factor in portal hypertensive gastropathy.
OBJECTIVE
Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa.


METHODS
Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(-)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication.


RESULTS
Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(-)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(-)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(-)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t.


CONCLUSIONS
Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.
Tsugawa
K
K
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Hashizume
M
M
Migou
S
S
Kishihara
F
F
Kawanaka
H
H
Tomikawa
M
M
Sugimachi
K
K
D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D001707:Biopsy, Needle; D004224:Diterpenes / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D005773:Gastroscopy; D006595:Hexosamines / Q000032:analysis; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D012039:Regional Blood Flow; D013272:Stomach Diseases / Q000188:drug therapy / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D016228:Endothelial Growth Factors; D006595:Hexosamines; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C031049:geranylgeranylacetone