Cavernous hypoxia is an important factor in the pathogenesis of vasculogenic erectile dysfunction (ED).
Therefore, the hypoxia-inducible gene expression system can be exploited to the 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 (Epo) 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. pRTP801-Luc and pEpo-SV-Luc significantly induced gene expression 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 may be a valuable tool for facilitating gene delivery into ischemic corpus cavernosum tissue resulting from vascular causes.
Written by:
Ryu JK, Lee M, Choi MJ, Kim HA, Jin HR, Kim WJ, Yin GN, Song KM, Kwon MH, Suh JK. Are you the author?
Reference: J Androl. 2012 Mar 8. Epub ahead of print.
doi: 10.2164/jandrol.111.016014
PubMed Abstract
PMID: 22403284
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