The specific expression of hypoxia inducible factor-1alpha 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-1α (HIF-1α) reflects the status of tissue ischaemia. Aim: To investigate the effect of NSAID administration on the expression of HIF-1α in human gastric mucosa. Methods: We employed 71 patients including 14 with NSAID administration. The HIF-1α expression was estimated by immunohistochemistry using monoclonal antibody (H1α67) 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-1α was mainly expressed in the nuclei of the surface epithelial cells and in the neck zone both by use of HI-3 and of H1α67. The expression of vascular endothelial growth factor correlated well with that of HIF-1α. The level of HIF-1α 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-la. Long-term administration of rebamipide reduced the level of HIF-1α. Conclusion: HIF-1α expression is a new biological marker of ischaemia especially in NSAID-related gastric lesions.