Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma

Abstract

Rationale: Subepithelial hyper-vascularity and angiogenesis in the airways are part of structural remodeling of the airway wall in asthma, but the effects of inhaled corticosteroids (ICS) on these are unexplored. Increased vascularity in asthma may contribute to a number of functional abnormalities. We have explored angiogenic modulation by ICS and its likely regulation via vascular endothelial growth factor (VEGF), its receptors and the angiopoietins.

Objectives: We have undertaken a placebo- controlled intervention study with ICS in asthma, examining vascularity, VEGF, its receptors, and angiopoietin-1 (Ang1). We aimed to assess which of these factors were changed in the asthmatic airways after ICS treatment.

Methods: We obtained airway wall biopsies, lavage fluid and cells from 35 mild asthmatics that were then randomised to either ICS or placebo for three months, after which bronchoscopy and sample collection were repeated.

Measurements: Immunohistochemistry and image analysis to obtain quantitative measures of vessels, angiogenic sprouts, VEGF, VEGFR1, VEGFR2 and Ang1 staining in airway biopsies. ELISA to assess VEGF concentrations in the lavage fluid.

Results: Vessel, VEGF and sprout staining were decreased after 3 months of ICS treatment. VEGF levels remained unchanged. VEGF receptors and Ang1 staining were not reduced after treatment.

Conclusions: Our findings support an effect of ICS in down regulating angiogenic remodeling in the airways in asthma, associated with decreasing VEGF activity within the airway wall. The post-ICS environment of the airways, with changes in the balance between VEGFR, its receptors, Ang1 and sprouts, appears to be less angiogenic than in untreated asthma.