Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma

Summary Background There is increasing in vitro evidence to support a role for vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, as a mediator of fibrosis associated with neovascularization. Objective We tested the hypothesis that VEGF is involved both in increased airway mucosal vascularity and in the subepithelial fibrosis of asthmatic patients. Methods Bronchial biopsies were performed in 24 asthmatic patients and eight healthy controls. Immunostaining, using computerized image analysis, was performed using monoclonal antibodies against VEGF1 cells, type IV collagen, to outline the basement membrane thickness, and tryptase and EG2, to identify mast cells and eosinophils, respectively. Results The counts of VEGF1 cells (Po0.05), mast cells and EG21 cells (both Po0.01) were higher in asthmatics than in controls. The number of vessels, the vascular area in the lamina propria, and the basement membrane thickness were significantly higher in asthmatics than in healthy volunteers (Po0.01). Moreover, in asthmatic patients, the number of VEGF1 cells was significantly related to the number of vessels (Po0.01), to mast cells (Po0.01) and to basement membrane thickness (Po0.01). A colocalization study also revealed that mast cells were a relevant cellular source of VEGF. High doses of inhaled fluticasone propionate significantly reduced VEGF1 cells (Po0.05), vessel number (Po0.05), vascular area (Po0.05) and basement membrane thickness (Po0.05) in a subgroup of asthmatic patients. Conclusions This study shows that VEGF, in addition to being involved in the vascular component of airway remodelling, may play a role in the thickening of the basement membrane in asthma. Keywords airway remodelling, asthma, bronchial biopsy, vascular endothelial growth factor Submitted 6 April 2005; revised 27 June 2005; accepted 15 July 2005