Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Abstract

Background. Living at a high plateau in a very hostile environment and low oxygen levels often leads to the development of high-altitude polycythemia (HAPC) and gastric mucosal lesions caused by high-level reactive oxygen species (ROS). Hypoxia-inducible factor-1A (HIF-1A) helps maintain oxygen homeostasis by promoting the transcription of various genes and can be affected by ROS levels. To evaluate the molecular mechanism by which HAPC causes the gastric mucosal lesions, the expression of HIF-1A was measured in Tibetans with HAPC and in healthy subjects. Ultrastructural, histopathological, and immunohistochemical analyses were performed in the gastric tissues of both groups, and the expression of HIF-1A in the gastric mucosa was detected using qPCR and Western Blot.Results. The microvessel density and average diameter of gastric mucosal vessels were significantly greater in the HAPC patients than in the healthy subjects (p< 0.05). The number of red blood cells in the gastric mucosa was also significantly higher in the HAPC group than in the healthy subjects (p< 0.05). In addition, the density of the mitochondrial vacuoles and endoplasmic reticulum and pathological apoptosis were significantly increased in the gastric cells from HAPC patients compared to those from the healthy subjects. The levels of ROS and HIF-1A in the gastric mucosa were increased in HAPC patients compared to those in controls (p< 0.05).Conclusions. An increased level of HIF-1A was associated with HAPC development in the stomach of Tibetans living at a high altitude. ROS upregulated the levels of HIF-1A. Thus, ROS-mediated HIF-1A signaling transduction may be the mechanism associated with HAPC-induced gastric lesions.