title: Up-regulation of thrombin activity induced by vascular endothelial growth factor in asthmatic airways.
abstract: BACKGROUND
  High expression of vascular endothelial growth factor (VEGF) induces subepithelial fibrosis associated with angiogenesis in patients with asthma. Thrombin is recognized as a new candidate mediating airway remodeling. Therefore, this study was designed to determine the role of up-regulated thrombin activity induced by VEGF on airway remodeling in patients with asthma.
  
  
  METHODS
  Levels of biochemical parameters in induced sputum were examined in 21 asthmatic patients and 11 normal control subjects.
  
  
  RESULTS
  Thrombin activity in induced sputum was significantly higher in asthmatic patients than in normal control subjects: median, 3.67 U/mL; range, 1.15 to 10.2 U/mL; vs median, 1.26 U/mL; range, 0.93 to 2.42 U/mL (p < 0.0001). In contrast, protein C activity in induced sputum was lower in asthmatic patients than in normal control subjects: median, 20%; range, 5 to 30%; vs 41%; range, 30 to 59% (p < 0.0001). VEGF level in induced sputum was positively correlated with thrombin activity in asthmatic patients (r = 0.55, p = 0.02), while inversely correlated with protein C activity (r = - 0.57, p = 0.01). Levels of basic fibroblast growth factor (bFGF), a major profibrotic factor, were also significantly higher in asthmatic patients than in normal control subjects. Moreover, thrombin activity was significantly correlated with bFGF level in asthmatic patients (r = 0.67, p = 0.003).
  
  
  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.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abenoku, Osaka, 545-8585, Japan. kanazawa-h@med.osaka-cu.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D008297:Male; D011486:Protein C / Q000378:metabolism; D013183:Sputum / Q000737:chemistry*; D013917:Thrombin / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D011486:Protein C; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013917:Thrombin