Gene therapy with an erythropoietin enhancer-mediated, hypoxia-inducible gene expression system in the corpus cavernosum of mice with high-cholesterol diet-induced erectile dysfunction.
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Cavernous hypoxia is an important factor in the pathogenesis of vasculogenic erectile dysfunction (ED). Therefore, the hypoxia-inducible gene expression system can be exploited as gene therapy for vasculogenic ED. This study was undertaken to examine the effectiveness of a hypoxia-inducible gene expression system, namely, the RTP801 promoter or the erythropoietin enhancer, in a mouse model of hypercholesterolemic ED in vivo and in primary cultured mouse cavernous endothelial cells in vitro. Two-month-old male C57BL/6 mice were fed a diet containing 4% cholesterol and 1% cholic acid, and age-matched control animals were fed a normal diet for 3 months. Mouse cavernous endothelial cells were isolated and cultured under normoxic or hypoxic conditions. After treatment of animals or endothelial cells with pSV-Luc, pRTP801-Luc, or pEpo-SV-Luc vector, gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. Plasmids pRTP801-Luc and pEpo-SV-Luc induced gene expression significantly in the hypercholesterolemic mice and in cavernous endothelial cells under hypoxia, and the highest gene expression was noted in the group treated with pEpo-SV-Luc. Gene expression was higher for more than 7 days in the hypercholesterolemic mice injected with pEpo-SV-Luc than in mice injected with pSV-Luc. As shown by immunohistochemistry, the gene expression area was also greater in the pEpo-SV-Luc group than in the pSV-Luc group, but the difference was not as great as that in luciferase activity. The hypoxia-specific gene expression system could be a valuable tool for facilitating gene delivery into ischemic corpus cavernosum tissue resulting from vascular causes. (+info)
Angiography and endovascular revascularization of pudendal artery atherosclerotic disease in patients with medically refractory erectile dysfunction.
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PURPOSE: To report a technique for endovascular treatment of pudendal artery stenoses in medically refractory erectile dysfunction. CASE REPORT: Three men with known peripheral arterial disease and erectile dysfunction that was non-responsive to treatment with phosphodiesterase inhibitors underwent angiography and stent placement of the pudendal artery. Stent placement was performed using standard endovascular techniques. All 3 patients reported significant improvement in erectile function following revascularization. CONCLUSION: Percutaneous treatment of pudendal artery stenoses with stents is feasible and offered significant benefit to these 3 patients. (+info)
Erectile dysfunction of vascular cause: statistical evaluation on the plurimetabolic syndrome's risk factors and their correlation with penile eco-doppler rates.
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INTRODUCTION: The Plurimetabolic Syndrome is a clustering of vascular risk factors (dyslipemia, abdominal perimeter, HTA and impaired glucose tolerance) with great importance in the development of cardiovascular disease (CVD) and diabetes (DM). CDV and DM are responsible for near 70% of the erectile dysfunction causes. Eco-doppler is the first line exam for the evaluation of cavernous arterial integrity. METHODS AND MATERIALS: A epidemiologic retrospective study and statistic evaluation of the risk factors was made from a population of 176 patients who were submitted to penile eco-doppler with a 12 MHz BK ultrasound. The procedure was done with 20 to 40 microg of prostaglandin E1 and by the some investigator. The criteria of ED of arterial origin were the peak systolic velocity (PSV) < 30 cm/seg and the resistance index (IR) < 0,75. For the ED of venous-occlusive origin was the peak diastolic velocity (PDV) > 10 cm/seg with normal PSV. The control group was the patients without risk factors and with normal eco-doppler values. RESULTS/CONCLUSION: The mean age was 49 (17-77) years old. The vascular diseases were present in 41% of the population. The venous-occlusive correspond to 11% of the diagnosis of vascular diseases and 89% to arterial origin. The PSV and the IR become lower with the age and the PDV has no variation (Spearman correlation coefficient, p < 0,001). The PSV and the IR become lower when the risk factors are present and when there are more than one risk factor (Mann-Whitney test, p < 0,001). The PDV had no variation. We were not able to prove the risk grade of the vascular factors analysed in the PSV and the IR (Kruskal-Wallis test, p = 0,2048). (+info)
Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage.
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Temporal changes in erectile function and endothelium-dependent relaxing response of corpus cavernosal smooth muscle after ischemia by ligation of bilateral internal iliac arteries in the rabbit.
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We aimed to elucidate the changes in the relaxation function of corpus cavernosal smooth muscle (CCSM) and erectile function using acute penile ischemic rabbits. Relaxation response to acetylcholine (Ach) was unchanged at 3 days after ischemia. The response to ACh had significantly decreased at 1 week, but had recovered completely at 4 weeks. The reaction to sodium nitroprusside and electrical field stimulation was unchanged by ischemia at all time points. Erectile function was changed in the same manner as the response of ACh. The endothelium-dependent relaxing responses of CCSM and erectile function were found to be initially decreased, but subsequently improved completely. (+info)