Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma
Article first published online: 9 NOV 2005
Clinical & Experimental Allergy
Volume 35, Issue 11, pages 1437–1442, November 2005
How to Cite
Chetta, A., Zanini, A., Foresi, A., D'Ippolito, R., Tipa, A., Castagnaro, A., Baraldo, S., Neri, M., Saetta, M. and Olivieri, D. (2005), Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma. Clinical & Experimental Allergy, 35: 1437–1442. doi: 10.1111/j.1365-2222.2005.02360.x
- Issue published online: 9 NOV 2005
- Article first published online: 9 NOV 2005
- Submitted 6 April 2005; revised 27 June 2005; accepted 15 July 2005
- airway remodelling;
- bronchial biopsy;
- vascular endothelial growth factor
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 VEGF+ 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 VEGF+ cells (P<0.05), mast cells and EG2+ cells (both P<0.01) 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 (P<0.01). Moreover, in asthmatic patients, the number of VEGF+ cells was significantly related to the number of vessels (P<0.01), to mast cells (P<0.01) and to basement membrane thickness (P<0.01). A colocalization study also revealed that mast cells were a relevant cellular source of VEGF. High doses of inhaled fluticasone propionate significantly reduced VEGF+ cells (P<0.05), vessel number (P<0.05), vascular area (P<0.05) and basement membrane thickness (P<0.05) 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.