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.
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.
Authors: Kenji Izuhara; Simon J Conway; Bethany B Moore; Hisako Matsumoto; Cecile T J Holweg; John G Matthews; Joseph R Arron Journal: Am J Respir Crit Care Med Date: 2016-05-01 Impact factor: 21.405
Authors: Thomas N Wight; Charles W Frevert; Jason S Debley; Stephen R Reeves; William C Parks; Steven F Ziegler Journal: Cell Immunol Date: 2016-12-23 Impact factor: 4.868
Authors: Jeroen J W Liesker; Nick H Ten Hacken; Mieke Zeinstra-Smith; Steven R Rutgers; Dirkje S Postma; Wim Timens Journal: Int J Chron Obstruct Pulmon Dis Date: 2009-04-15