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Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model

International Journal of Impotence Research volume 20, pages 307–314 (2008)Cite this article

Abstract

Erectile dysfunction (ED) is a cause of decreased quality of life in more than 70% of diabetic men. Vascular endothelial growth factor (VEGF) has shown to improve overall endothelial and smooth muscle cell dysfunction in models of ED. We describe a novel technique for nonviral, in vivo gene transfection of VEGF in the rat corpus cavernosum. Diabetic rats were transfected with DNA encoding a fusion VEGF/green fluorescent protein (GFP) complex and fluorescence microscopy was used to monitor the expression of VEGF–GFP fusion protein. Western blot and PCR analyses confirmed the expression of the GFP–VEGF fusion protein and mRNA. Functional studies using cavernous nerve stimulation revealed maximal intracavernous pressures (ICPs) of 63.1 mm Hg, and 30.7 mm Hg in the normal and diabetic control groups, respectively, and 47.4 mm Hg in VEGF–GFP-transfected diabetic group. Immunohistochemical analysis of the cavernosal tissue from transfected rats showed increased smooth muscle content compared with the diabetic control group. We show for the first time in our animal model that expression of the transfected VEGF in cavernosal tissue leads to an overall improvement of maximal ICP and smooth muscle content. On the basis of these results, it is tempting to speculate that our nonviral vector system offers an excellent system for gene delivery into cavernosal tissue, and that VEGF gene therapy using this system could be useful in improving erectile function in diabetic men.

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Acknowledgements

This study was supported in part by UCDHSC SOM and the Department of Surgery AEF grant support.

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Authors and Affiliations

  1. Division of Urology—Department of Surgery, Signal Transduction and Molecular Urology Laboratory, Program in Urosciences, School of Medicine, Denver, Colorado, USA

    J E Dall'Era, R B Meacham, J N Mills, S Koul, S N Carlsen, J B Myers & H K Koul

  2. University of Colorado Comprehensive Cancer Center, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA

    H K Koul

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  1. J E Dall'Era
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  2. R B Meacham
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  3. J N Mills
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  4. S Koul
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  5. S N Carlsen
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  6. J B Myers
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  7. H K Koul
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Correspondence to H K Koul.

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Dall'Era, J., Meacham, R., Mills, J. et al. Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model. Int J Impot Res 20, 307–314 (2008). https://doi.org/10.1038/ijir.2008.1

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