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Periadventitial angiopoietin-1 gene transfer induces angiogenesis in rabbit carotid arteries

A Corrigendum to this article was published on 08 August 2005

Abstract

This study was performed to evaluate angiogenic responses of angiopoietin-1 (Ang1) in vivo after adenovirus-mediated gene transfer in the periadventitial space of the rabbit carotid arteries using a collar technique. Adenoviruses encoding LacZ and vascular endothelial growth factor (VEGF) receptor-1-Ig fusion protein (VEGF-R1-Ig) adenoviruses were used as controls. Increased neovessel formation was seen in adventitia of the Ang1 transduced arteries 7 days after the gene transfer. Neovessels in the Ang1 transduced arteries were large in size and well perfused. Ang1 binds to Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domain) receptors, which were expressed in the endothelium of the neovessels. When VEGF-R1-Ig was used with Ang1, it resulted in a decrease in the number of neovessels, which implies that VEGF-A or some other VEGF-R1 ligand(s) play a crucial role in angiogenesis occurring in response to Ang1. There were no significant differences in the total number of capillaries in the adventitia of the VEGF-R1-Ig transduced arteries as compared to LacZ controls. Neointima formation was not increased in the Ang1 transduced arteries as compared to the controls. We conclude that in the periadventitial space Ang1 shows angiogenic activity and is a potentially useful factor for the induction of therapeutic vascular growth in vivo.

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Acknowledgements

This study was supported by grants from Finnish Foundation for Cardiovascular Research, Finnish Academy and European Union (QLK3-CT-2002-01955). We thank Mr Tommi Heikura, Ms Anne Martikainen and Ms Mervi Nieminen for excellent technical assistance and Ms Marja Poikolainen for help in preparation of the manuscript.

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Bhardwaj, S., Roy, H., Kärpänen, T. et al. Periadventitial angiopoietin-1 gene transfer induces angiogenesis in rabbit carotid arteries. Gene Ther 12, 388–394 (2005). https://doi.org/10.1038/sj.gt.3302426

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