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Published ahead of print on March 9, 2006, doi:10.1164/rccm.200507-1105OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 11, June 2006, 1201-1207

A more recent version of this article appeared on June 1, 2006
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Submitted on July 18, 2005
Accepted on March 8, 2006

Increased Vascular Endothelial Growth Factor and Receptors: Relationship to Angiogenesis in Asthma

Bryce N Feltis1*, Dharshini Wignarajah2, Ling Zheng2, Chris Ward2, David Reid1, Richard Harding2, and E. Haydn Walters1

1 Cardio-Respiratory Research Group, University of Tasmania, Hobart, Tasmania, Australia, 2 Department of Medicine and Physiology, Monash University, Melbourne, Victoria, Australia

* To whom correspondence should be addressed. E-mail: bryce_feltis{at}hotmail.com.

Rationale: Increased vascularity is a feature of airways remodelling in asthma with the potential to contribute to a number of functional abnormalities in this chronic disease. Whilst various growth factors have been implicated in modulating vascularity, the important contributors in vivo are still being elucidated. The most likely candidate is vascular endothelial growth factor (VEGF). Objectives: We have examined VEGF and its receptors, VEGFR1 and VEGFR2, and angiopoietin-1 (ang1) in the airways of asthmatic subjects and contrasted these to normal controls. We aimed to explore whether these powerful angiogenic factors were expressed at elevated levels in the asthmatic airways. Methods: We obtained biopsy and broncho-alveolar lavage (BAL) from 35 mild to moderate asthmatic subjects and 22 normal controls. Measurements: We performed immunohistochemistry and image analysis to obtain quantitative measures of VEGF, VEGFR1, VEGFR2 and Ang1 staining in airway biopsies and ELISA to assess VEGF concentration in the BAL. Results: VEGF staining and BAL VEGF levels were elevated in asthmatics and related to the number of vessels; Ang1 staining was similarly increased. VEGFR1 was slightly higher in asthmatics and the ratio of VEGFR1:VEGFR2 was significantly higher in asthmatics. We observed angiogenic sprouts (ie. early forming vascular structures) that were increased in number in asthmatic subjects. Conclusions: Our findings suggest that VEGF, its receptors and Ang1, are likely to be important in the vascular changes in the airways of asthmatic patients. Further, there are observable structures in the vessel walls in asthmatic airways that could present ongoing evidence of increased angiogenic activity.
Key words: VEGF, vascularity, blood vessels, sprouting




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