[Potential mechanisms of airway remodeling initiated by activated thrombin in asthma].

Background: High expression of vascular endothelial growth factor (VEGF) induces subepithelial fibrosis associated with angiogenesis in asthma. Thrombin is recognized as a new candidate mediating airway remodeling. Therefore, this study was designed to determine the potential mechanisms of airway remodeling initiated by activated thrombin in asthma.

Methods: Levels of biochemical parameters in induced sputum were examined in 21 asthmatic patients and 11 normal controls.

Results: Thrombin activity in induced sputum was significantly higher in asthmatic patients than in normal controls (normal controls: median [range] 1.26 (0.93-2.42) U/mL; asthmatic patients: 3.67 (1.15-10.2) U/mL, p < 0.0001). VEGF level in induced sputum was positively correlated with thrombin activity in all study subjects. Levels of basic fibroblast growth factor (bFGF), which is a major profibrotic factor, were also significantly higher in asthmatic patients than in normal controls. Moreover, thrombin activity was significantly correlated with bFGF level in all study subjects. We also observed a significant correlation between bFGF and procollagen type III peptide level.

Conclusion: Increase in VEGF level leads to up-regulation of thrombin activity in asthmatic airways, and this elevated thrombin activity induces elevation of bFGF level. It will become to be a new strategy of asthma therapy to attenuate thrombin activity for the regulation of airway remodeling.