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Sources of Funding: None

Introduction

Small non-coding RNAs, known as microRNAs (miR), have been shown to play a key role in the post-transcriptional regulation of gene expression. One of these, miR-93, has been shown to promote endothelial cell proliferation, survival, resistance to apoptosis, and enhanced vascular stability, especially with its ability to down-regulate VEGF. We sought to evaluate the presence and role of miR-93 in the mouse corpus cavernosum in mice with diet-induced hyperinsulinemia, a state known to predispose to erectile dysfunction (ED).

Methods

Studies from our group have shown that feeding C57BL/6 mice a high fat diet (HFD) where 45% of its daily calories come from fat caused obesity, hyperglycemia, and insulin-resistance. We first examined the corpus cavernosum in these mice to look for the effects of the hyperinsulinemic state. We then compared miR-93 expression in the corpora of mice with and without a HFD. Finally, intracorporal injections of pre-miR-93 were performed in some of the mice, and levels of three reported miR-93 targets were recorded.

Results

With regard to our first aim to characterize the corpus cavernosum of HFD rats, we found that a number of findings were consistent with ED including: a) abnormalities in corporal endothelium-dependent and endothelium-independent vasoreactivity; b) a decrease in the ratio of the smooth muscle to collagen content, c) a reduction in NADPH diaphorase staining (measure of bioavailable NO) and d) increases in apoptosis, as measured by TUNEL staining. Results for parts two and three are summarized in Figure 5.

Conclusions

These results demonstrate a few key factors. First, that the HFD mice tend to exhibit corporal changes consistent with vasculogenic ED. Second, that miR-93 expression is increased in these mice, likely as a response to elevated VEGF and other vasculopathic factors. And third, that injections of miR-93 precursors can alter gene expression of these known vasculopathic factors. This may provide a novel therapeutic target for vasculogenic ED with futher study.

Funding

None