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 microg/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).


CONCLUSIONS
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.
Asai
Kazuhisa
K
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Kanazawa
Hiroshi
H
Otani
Kenichiro
K
Shiraishi
Satoshi
S
Hirata
Kazuto
K
Yoshikawa
Junichi
J
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001507:Beclomethasone / Q000627:therapeutic use; D003094:Collagen / Q000032:analysis* / Q000037:antagonists & inhibitors; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000032:analysis* / Q000037:antagonists & inhibitors; D008297:Male; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000032:analysis* / Q000037:antagonists & inhibitors; D012016:Reference Values; D013183:Sputum / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018927:Anti-Asthmatic Agents; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen; D001507:Beclomethasone