Imbalance between vascular endothelial growth factor and endostatin levels in induced sputum from asthmatic subjects

Background: Angiogenesis has recently attracted considerable attention as a component of airway remodeling in bronchial asthma. Vascular endothelial growth factor (VEGF) is highly expressed in asthmatic airways, and its contribution to airway remodeling has been reported. Although angiogenesis is regulated by a balance of angiogenic and antiangiogenic factors, the relative levels of antiangiogenic factors in asthmatic airways have not been evaluated. Objective: We sought to determine whether an imbalance between angiogenic and antiangiogenic factors exists in asthmatic airways. Methods: We simultaneously measured VEGF and endostatin levels and evaluated their correlation and balance in induced sputum from 18 steroid-naive asthmatic subjects and 11 healthy control subjects. After initial sputum induction, asthmatic subjects underwent 8 weeks of inhaled beclomethasone dipropionate (BDP; 800 mug/d) therapy, and sputum induction was then repeated. Results: VEGF and endostatin levels in induced sputum were significantly higher in asthmatic subjects than in control subjects (P < .001). There was a significant correlation between VEGF and endostatin levels in both control subjects (r = 0.995, P < .001) and asthmatic subjects (r = 0.923, P < .001). Moreover, the VEGF/endostatin level ratio in asthmatic subjects was significantly higher than that in control subjects (P < .0001). After 8 weeks of inhaled BDP therapy, the VEGF level in induced sputum in asthmatic subjects was significantly decreased (P < .001), whereas the endostatin level was not. A correlation between VEGF and endostatin levels existed even after BDP therapy (r = 0.861, P < .001). Moreover, the VEGF/endostatin level ratio was significantly decreased to the same level as in the control subjects after BDP therapy (P < .0001). Conclusion: There was an imbalance between VEGF and endostatin levels in induced sputum from asthmatic subjects. This imbalance might play an important role in the pathogenesis of bronchial asthma through its effects on angiogenesis.