Original Paper

Spatial and Phenotypic Characterization of Vascular Remodeling in a Mouse Model of Asthma
Xinming Su^{a, d}, Namiko Taniuchi^a, Enjing Jin^a, Masakazu Fujiwara^a, Lei Zhang^a, Mohammad Ghazizadeh^a, Hiroyuki Tashimo^b, Naomi Yamashita^c, Ken Ohta^b, Oichi Kawanami<sup>a

a</sup>Department of Molecular Pathology, Institute of Development and Aging Sciences, Nippon Medical School, Kawasaki, and
^bDepartment of Medicine, Teikyo University School of Medicine, and
^cMusashino University, Tokyo, Japan;
^dInstitute of Respiratory Diseases, China Medical University, Shenyang, China

Address of Corresponding Author

Pathobiology 2008;75:42-56 (DOI: 10.1159/000113794)

  Key Words

• Asthma
• Lung
• Mouse model
• Phenotypes
• Trachea
• Vascular remodeling

  Abstract

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 -smooth muscle actin and desmin in the mural cells of the vessels, suggesting a phenotypic and functional transformation. The mRNA levels of VEGF isoforms, VEGF₁₆₄ and VEGF₁₈₈, 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.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Prof. Oichi Kawanami, MD
Department of Molecular Pathology
Institute of Development and Aging Sciences, Nippon Medical School
1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533 (Japan)
Tel. +81 44 733 1821, Fax +81 44 733 1293, E-Mail kawanami@nms.ac.jp

  Article Information

Received: July 17, 2007
Accepted after revision: November 12, 2007
Published online: March 11, 2008
Number of Print Pages : 15
Number of Figures : 9, Number of Tables : 1, Number of References : 35