Role of Vascular Endothelial Growth Factor in Portal Hypertensive Gastropathy

Abstract

Background and Aims: 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. Method: 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. Conclusion: 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.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

“…Most studies reported decreased mucosal blood flow in patients with PHG [76,[128][129][130][131] , whereas several studies reported increased gastric mucosal blood flow in experimental animals and in humans with PHG [132][133][134][135][136] . Makhija et al [118] described in PHG a decrease in gastric mucosal blood flow, an increase in the submucosal and muscular layer blood flow, and a net increase in total gastric blood flow.…”

“…This phenomenon may decrease the reparative capacity of PHG mucosa [127] . However, Tsugawa et al [136] reported humans with PHG had increased vascular endothelial growth factor (VEGF), a potent angiogenic factor. Additionally, rats with PHG had a significant decrease in the SaO2 and PaO2 of the arterial blood gas, and increased levels of VEGF, proliferating cell nuclear antigen (PCNA) expression, and gastric mucosal blood flow in gastric mucosa.…”

“…Teprenone: In a controlled clinical trial, teprenone (geranylgeranyl acetone) administered to 15 patients with PHG decreased VEGF and hexosamine content in the gastric antrum, and thereby significantly decreased the severity of PHG [136] . Among these 15 treated patients, one patient decreased from severe to moderate PHG and another patient decreased from moderate to mild PHG [180] .…”

Lesiones vasculares gástricas en la cirrosis: gastropatía y ectasia vascular antral

“…Algunos autores indican que un aumento de los niveles locales del factor de crecimiento vascular epidérmico (VEGF) alteraría la permeabilidad vascular, aumentando la fragilidad mucosa gástrica y el riesgo de lesión 30,31 .…”

Angiogenesis in Portal Hypertension: Involvement in Increased Splanchnic Blood Flow and Collaterals?

“…The expression of VEGF in portal hypertensive gastric mucosa, whether in patients or in animal models, is significantly increased (23,24). The question remains whether angiogenesis is also involved in portal hypertensive gastropathy, commonly recognized in patients with PHT.…”