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

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 transfec...

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Bibliographic Details
Published in:	International journal of impotence research Vol. 20; no. 3; pp. 307 - 314
Main Authors:	Dall'Era, J E, Meacham, R B, Mills, J N, Koul, S, Carlsen, S N, Myers, J B, Koul, H K
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-05-2008 Nature Publishing Nature Publishing Group
Subjects:	Animals Biological and medical sciences Blotting, Western Care and treatment Diabetes Diabetes Mellitus Diabetes. Impaired glucose tolerance Diabetic Angiopathies Endocrine pancreas. Apud cells (diseases) Endocrinopathies Erectile dysfunction Erectile Dysfunction - etiology Erectile Dysfunction - therapy Etiopathogenesis. Screening. Investigations. Target tissue resistance Gene Expression Gene therapy Genetic aspects Genetic Therapy - methods Genetic Vectors Gynecology. Andrology. Obstetrics Health aspects Impotence Male Medical sciences Medicine Medicine & Public Health original-article Penile Erection - genetics Physiological aspects Polymerase Chain Reaction Proteins Rats Rats, Sprague-Dawley Reproductive Medicine Risk factors rology Smooth muscle Transfection - methods Treatment Outcome Urology Vascular endothelial growth factor Vascular Endothelial Growth Factor A - therapeutic use United States gene therapy diabetic model VEGF erectile dysfunction Endocrinopathy Delivery system Andrology Animal model Erection disorders Rat Erection Diabetes mellitus Sexual dysfunction Rodentia Genetic transfer Vertebrata Mammalia Vascular endothelium growth factor Treatment Gene therapy Male genital diseases
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0955-9930 1476-5489
DOI:	10.1038/ijir.2008.1