The specific expression of Hypoxia Inducible Factor-1α in human gastric mucosa induced by nonsteroidal anti-inflammatory drugs

Background: Hypoxia is a cause of gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The expression of hypoxia inducible factor-1alpha (HIF-1alpha) reflects the status of tissue ischaemia. Aim: To investigate the effect of NSAID administration on the expression of HIF-1alpha in human gastric mucosa. Methods: We employed 71 patients including 14 with NSAID administration. The HIF-1alpha expression was estimated by immunohistochemistry using monoclonal antibody (H1alpha67) and raised antiserum (HI-3). Vascular endothelial growth factor expression was also examined by immunohistochemistry. HI-3 recognized hypoxia-induced protein in HeLa cells. Results: In human gastric mucosa, HIF-1alpha was mainly expressed in the nuclei of the surface epithelial cells and in the neck zone both by use of HI-3 and of H1alpha67. The expression of vascular endothelial growth factor correlated well with that of HIF-1alpha. The level of HIF-1alpha in the surface epithelium was significantly higher in patients with administration of NSAIDs than those without NSAID use (P < 0.001) both in the gastric corpus and antrum. Helicobacter pylori infection did not affected the levels of HIF-1 alpha. Long-term administration of rebamipide reduced the level of HIF-1 alpha. Conclusion: HIF-1 alpha expression is a new biological marker of ischaemia especially in NSAID-related gastric lesions.