[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.


CONCLUSIONS
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.
Kanazawa
Hiroshi
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University. kanazawa-h@med.osaka-cu.ac.jp
Kyoh
Shigenori
S
Tochino
Yoshihiro
Y
Kodama
Toyoki
T
Asai
Kazuhisa
K
Hirata
Kazuto
K
D000328:Adult; D001249:Asthma / Q000473:pathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006801:Humans; D008297:Male; D012137:Respiratory System / Q000473:pathology*; D013183:Sputum / Q000737:chemistry; D013917:Thrombin / Q000032:analysis / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013917:Thrombin