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Roles of Angiopoietin-1 and Angiopoietin-2 on Airway Microvascular Permeability in Asthmatic Patients^*

^* From the Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Correspondence to: Hiroshi Kanazawa, MD, PhD, Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1–4-3, Asahi-machi, Abenoku, Osaka, 545-8585, Japan; e-mail: kanazawa-h{at}med.osaka-cu.ac.jp

Abstract

Background: Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma.

Methods: Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 µg/d) or montelukast (10 mg) for 12 weeks.

Results: VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level.

Conclusions: Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.

Key Words: airway remodeling • bronchial asthma • vascular endothelial growth factor