Gene transfer of vasoactive intestinal polypeptide into the penis improves erectile response in the diabetic rat

Zhang, Shen; Wang, Hua; Lu, Yingli; Zhou, Xin; Chen, Shan-Wen; Chen, Zhao-Dian

doi:10.1111/j.1464-410x.2005.05422.x

Cited by 32 publications

(20 citation statements)

References 49 publications

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“…Several genes have been targeted for possible therapies, including hSlo calcium-sensitive K þ channel, endothelial nitric oxide synthase, (neuronal nitric oxide synthase , vascular endothelial growth factor (VEGF), vasoactive intestinal peptide and brain-derived neurotrophic factor. [2][3][4][5][6][7][8] Many techniques of gene delivery systems exist, each with their respective advantages and disadvantages. Viral delivery systems remain the most widely used in research today.…”

Section: Introductionmentioning

confidence: 99%

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

Dall’Era¹,

Meacham²,

Mills³

et al. 2008

Int J Impot Res

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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-GFPtransfected 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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Section: Introductionmentioning

confidence: 99%

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

Dall’Era¹,

Meacham²,

Mills³

et al. 2008

Int J Impot Res

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show abstract

“…Several groups have used vectors to insert genes for vascular endothelial growth factor, nitric oxide synthase, preprocalcitonin gene-related peptide, and vasoactive intestinal peptide into the corporal bodies of rodents. [15][16][17][18][19][20][21] These studies all have demonstrated improved erections and cavernous pressures in response to stimuli in the rat. However, these strategies have relied on vectors inserting genes into the host chromosomes, and this introduces the potential for insertion into unintended targets.…”

Section: Gene Therapy For Edmentioning

confidence: 92%

Ion Channel Gene Therapy for Smooth Muscle Disorders: Relaxing Smooth Muscles to Treat Erectile Dysfunction

Schiff

Melman

2006

ASSAY and Drug Development Technologies

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The promise of gene therapy to treat diseases remains largely unfulfilled. Past setbacks and the complexity of the delivery systems used, in terms of both targeting the appropriate cells and inducing expression of products at therapeutic levels, thus far have prevented significant success for gene therapy. Smooth muscle disorders represent a unique target for gene therapy. In many cases, smooth muscle is readily accessible and, to induce a therapeutic effect, will not require very high levels of gene product expression. This allows a lower efficiency of gene transfer to be successful. With these important features in mind, we believe that naked DNA transfer of potassium ion channels represents a novel and successful way to treat smooth muscle disorders. Herein, we present a rationale for treating erectile dysfunction, a smooth muscle disorder of the cavernosal bodies of the penis, with naked DNA gene transfer therapy. By inserting the hSlo gene, which codes for Maxipotassium channels, into smooth muscle cells, we can improve smooth muscle relaxation in the corporal bodies and thus improve erectile function. This method of gene transfer has proven to be safe and effective for erectile dysfunction, and human trials are ongoing.

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“…Intracavernous injection of adenovirus vector prepro-CGRP into aged rats resulted in increased levels of CGRP protein and cAMP, as well as higher ICP on cavernosal nerve stimulation compared to untreated control patients 5 days after treatment [71]. Vasoactive intestinal peptide (VIP) is another modulator of smooth muscle tone, and transfection of penile corpora cavernosa with pcDNA3/VIP cDNA in STZ-diabetic rats resulted in higher ICP and sustained expression of VIP mRNA for 2 weeks or more in the penis in vivo [72].…”

Section: Modulator Of Ion Channels In Smooth Muscle Cellsmentioning

confidence: 95%

Emerging and Novel Therapeutic Approaches in the Treatment of Male Erectile Dysfunction

Chung

Brock

2011

Curr Urol Rep

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Over the past few decades, a dramatic increase in our understanding of the pathophysiology of penile erection has occurred. The advent of phosphodiesterase type 5 inhibitors has revolutionized the treatment of erectile dysfunction (ED), while the introduction of modern penile prosthesis has almost completely replaced the need for vascular surgery. Despite the efficacy of current therapeutic options for ED, they are not without limitations and remain insufficient to address the growing patient population and various underlying medical conditions. Newer and novel ED therapies aspire to treat underlying microvascular abnormalities, prevent cavernosal fibrosis, promote endothelial revascularization, modulate neurohormonal pathways, and regenerate new penile tissue.

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Gene transfer of vasoactive intestinal polypeptide into the penis improves erectile response in the diabetic rat

Cited by 32 publications

References 49 publications

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

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

Ion Channel Gene Therapy for Smooth Muscle Disorders: Relaxing Smooth Muscles to Treat Erectile Dysfunction

Emerging and Novel Therapeutic Approaches in the Treatment of Male Erectile Dysfunction

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