Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma.
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.
Chetta
A
A
Department of Clinical Sciences, Section of Respiratory Diseases, University of Parma, Parma, Italy. chetta@unipr.it
Zanini
A
A
Foresi
A
A
D'Ippolito
R
R
Tipa
A
A
Castagnaro
A
A
Baraldo
S
S
Neri
M
M
Saetta
M
M
Olivieri
D
D
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001485:Basement Membrane / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D001706:Biopsy / Q000379:methods; D001980:Bronchi / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D001999:Bronchoscopy / Q000379:methods; D002452:Cell Count; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D009092:Mucous Membrane / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000730:Androstadienes; D001993:Bronchodilator Agents; D042461:Vascular Endothelial Growth Factor A; D000068298:Fluticasone