Increased Vascular Endothelial Growth Factor and Hypoxia Inducible Factor-1α Transcription in Acquired Sporadic Gastric Angiodysplasia

Abstract

Purpose: To study the role of the angiogenic factors, Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-1-alpha (HIF 1α) in the etiopathogenesis of gastric arteriovenous malformations. Methods: 9 patients with symptomatic sporadic acquired gastric angiodysplasia were included in the study. Mucosal biopsies were obtained from 3 locations: 0.5, 5 and 10 cm away from the lesion and mRNA was prepared for analysis of VEGF and HIF 1α expression using quantitative real time PCR. As control, biopsies of the antrum were obtained from 9 other patients with no gastric lesions but who were undergoing endoscopy for other reasons. Results: As compared with controls, mRNA levels of VEGF were increased 8-fold (95% confidence interval 5.55–10.45; p < 0.001) and those of HIF 1a, 3.4- fold (95% confidence interval 2.46–4.41; p < 0.001) in the mucosa immediately adjacent to the arteriovenous malformations. There was also a statistically significant correlation between HIF1 α and VEGF expression (r = 0.44, p= 0.05). Further, there was a clear gradient of expression with mRNA levels of both factors decreasing markedly with increasing distance away from the lesion. Conclusions: The expression of VEGF and HIF 1α is increased near sporadic acquired angiodysplastic lesions of the stomach, implying a possible causative effect. To our knowledge this is the first demonstration of a putative role for HIF1a in gastrointestinal arteriovenous malformations.