Expression of vascular endothelial growth factor and hypoxia-inducible factor in the airway of asthmatic patients

Background: Vascular endothelial growth factor (VEGF) is a potent proangiogenic cytokine, and it also increases vascular permeability. It is well known that VEGF levels are increased in the airway of asthmatic patients. Hypoxia-inducible factor (HIF) induces a rapid and strong increase in VEGF expression. Objectives: To evaluate the relationship between VEGF level and clinical characteristics and to determine whether VEGF expression is associated with HIF expression in asthmatic patients. Methods: Bronchoscopy was performed on 30 asthmatic patients and 14 control subjects. The concentration of VEGF in the bronchoalveolar lavage fluid (BALF) was examined using enzyme-linked immunosorbent assay. We measured VEGF, HIF-1α, and HIF-2α expression on biopsy specimens by means of immunoreactivity. Results: The VEGF level in the BALF was significantly higher in asthmatic patients than in controls. The VEGF level correlated with eosinophil counts in the BALF in asthmatic subjects (r = 0.501; P < .01). However, the VEGF level did not correlate with percentage of forced expiratory volume in 1 second and airway hyperresponsiveness. Asthmatic patients exhibited higher VEGF, HIF-1α, and HIF-2α immunoreactivity in the submucosa than did controls. Furthermore, VEGF expression correlated significantly with HIF-1α (r = 0.614; P = .02) and HIF-2α (r = 0.881; P = .001) expression. Conclusion: These findings suggest that VEGF may play an important role in inflammation and that VEGF level is related to HIF in bronchial asthma.