The effects of budesonide on angiogenesis in a murine asthma model.

introductionThe aim of this study is to determine the effects and mechanisms of budesonide on angiogenesis in a murine asthma model. MATERIAL AND

methodsMURINE ASTHMA MODELS WERE ESTABLISHED AND MICE WERE DIVIDED INTO THREE GROUPS: the model group (OVA-sensitized and challenged mice), the BUD group (budesonide-treated mice) and the PBS group (normal control mice). Mice in the BUD group were administered with inhaled budesonide (100 µg/kg) daily. The effects on airway inflammation, angiogenesis, expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were examined.

resultsAdministration of budesonide ameliorated allergic airway inflammation (2.90 ±0.18 vs. 4.80 ±0.20, p < 0.01) and significantly reduced the percentage vascularity (0.78 ±0.14 vs. 2.83 ±0.90, p < 0.01) compared with those in the asthmatic model mice. It also reduced the expression of HIF-1α (immunohistochemistry results: 71.70 ±1.40 vs. 89.60 ±0.79, p < 0.001; western blotting results: 0.88 ±0.41 vs. 0.97 ±0.47, p < 0.05), as well as that of VEGF (immunohistochemistry results: 26.30 ±1.03 vs. 93.30 ±1.54, p < 0.001; western blotting results: 1.12 ±0.22 vs. 2.08 ±0.30, p < 0.01). Percentage vascularity had positive correlation with both HIF-1α (r = 0.785, p < 0.01) and VEGF (r = 0.693, p < 0.01) expression. Furthermore, there is positive relationship between HIF-1α and VEGF expression (r = 0.641, p < 0.05).

conclusionsThe results demonstrate that budesonide has an important inhibitory effect on angiogenesis in asthma. Inhaled administration of budesonide achieved anti-angiogenic activity through inhibition of HIF-1α and VEGF expression. The results support a potential anti-remodeling role for budesonide in the treatment of human asthma.