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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

Title
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
Author
이민형
Keywords
Hypoxia response element; hypercholesterolemia; vector
Issue Date
2012-09
Publisher
Wiley
Citation
Journal of Andrology, Sep-Oct 2012, 33(5), P.845-853, 9p.
Abstract
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.
URI
https://onlinelibrary.wiley.com/doi/abs/10.2164/jandrol.111.016014
ISSN
0196-3635
DOI
10.2164/jandrol.111.016014
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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