Increased Vascular Endothelial Growth Factor and Receptors: Relationship to Angiogenesis in Asthma
Feltis, BN and Wignarajah, D and Zheng, L and Ward, C and Reid, DW and Harding, R and Walters, EH, Increased Vascular Endothelial Growth Factor and Receptors: Relationship to Angiogenesis in Asthma, American Journal of Respiratory and Critical Care Medicine, 173, (11) pp. 1201-1207. ISSN 1073-449X (2006) [Refereed Article]
Rationale: Increased vascularity is a feature of airway remodeling in asthma with the potential to contribute to a number of functional abnormalities in this chronic disease. Although 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 subjects with asthma and contrasted these results with findings in normal control subjects. We aimed to explore whether these powerful angiogenic factors were expressed at elevated levels in asthmatic airways. Methods: We obtained biopsy and bronchoalveolar lavage samples from 35 subjects with mild to moderate asthma and from 22 normal control subjects. 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 bronchoalveolar lavage fluid. Results: VEGF staining and VEGF levels in bronchoalveolar lavage fluid were elevated in the airways of subjects with asthma and were related to the number of vessels; Ang1 staining was similarly increased. VEGFR1 was slightly higher in subjects with asthma and the VEGFR1:VEGFR2 ratio was significantly higher in subjects with asthma. We observed angiogenic sprouts (i.e., early-forming vascular structures) that were increased in number in subjects with asthma. Conclusions: Our findings suggest that VEGF, its receptors, and Ang1 are likely to be important in vascular changes in the airways of patients with asthma. Further, there are observable structures in the vessel walls of asthmatic airways that could present ongoing evidence of increased angiogenic activity.