Spatial and phenotypic characterization of vascular remodeling in a mouse model of asthma.
Asthma is a chronic inflammatory disease characterized by airway wall remodeling in which vascular remodeling is thought to be a main contributor. Vascular endothelial growth factor (VEGF) is known as a major regulator of angiogenesis and enhancer of vascular permeability. Here, we define the spatial nature of vascular remodeling and the role of VEGF and its receptors (Flt-1 and Flk-1) in the allergic response in mice (A/J) susceptible to the development of allergen-induced airway hyperresponsiveness using morphometric and quantitative approaches. Increased vascularity, vasodilatation, and endothelial cell proliferation were found in the tracheal and bronchial walls in the early and late phases of asthma. Vascular changes were observed not only in small vessels but also in larger vessels. In contrast to normal control, lung tissue from the asthma model showed dual expression for CD31 and von Willebrand factor in the endothelial cells and alpha-smooth muscle actin and desmin in the mural cells of the vessels, suggesting a phenotypic and functional transformation. The mRNA levels of VEGF isoforms, VEGF(164) and VEGF(188), were significantly increased in the tracheal and lung tissue, respectively. In addition, the mRNA level of VEGF receptor Flk-1 was significantly increased in the trachea. These results establish the existence of vascular remodeling in the airways in a mouse model of allergic asthma and support a key role for the expression of unique VEGF isoform genes as mediators of structural changes.
Su
Xinming
X
Department of Molecular Pathology, Institute of Development and Aging Sciences, Nippon Medical School, Kawasaki, China.
Taniuchi
Namiko
N
Jin
Enjing
E
Fujiwara
Masakazu
M
Zhang
Lei
L
Ghazizadeh
Mohammad
M
Tashimo
Hiroyuki
H
Yamashita
Naomi
N
Ohta
Ken
K
Kawanami
Oichi
O
D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D051379:Mice; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014132:Trachea / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D014841:von Willebrand Factor; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2