SFEBES2014 Poster Presentations Steroids (39 abstracts)
Endogenous androgen-mediated modulation of neointima formation is independent of vascular androgen receptor
Junxi Wu 1, , Patrick Hadoke 2 , Iris Mair 2 , Win Gel Lim 2 , Eileen Millar 2 , Laura Milne 1 , Martin Denvir 2 & Lee Smith 1
1The Queen’s Medical Research Institute, MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, UK; 2The Queen’s Medical Research Institute, BHF Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK.
Aims: Low circulating testosterone levels are associated with increased cardiovascular risk and there is evidence that androgens inhibit arterial lesion formation. This investigation addressed the hypothesis that androgens directly inhibit neointimal lesion formation by stimulation of vascular androgen receptor.
Methods and results: Mice were generated with selective deletion of androgen receptor from vascular (endothelial or smooth muscle) cells. Castration in WT mice produced a modest increase in neointimal lesion formation following denuding (wire) injury of the mouse femoral artery (sham vs castration: 2.4×107±4.5×106 vs 3.9×107±4.9×106 μm3, P=0.0386, n=9–10), but not after non-denuding (ligation) injury. Pharmacological androgen replacement (testosterone, 10 mg/kg per day, via SUBCUTANEOUS minipump) in castrated mice did not, however, reduce lesion size (castration vs testosterone: 3.5×107±3.1×106 vs 3.0×107±3.2×106 μm3, P=0.2395, n=8–9). Selective deletion of androgen receptor from vascular cells had no effect on circulating testosterone levels or seminal vesicle weight but produced a modest increase (~8–12 mmHg) in blood pressure. Deletion of androgen receptor from smooth muscle cells reduced (5.3±0.33 vs 2.8±0.55 mN/mm, P<0.0001, n=7–9) phenylephrine-mediated contraction in isolated femoral arteries. Selective deletion of androgen receptor from endothelial cells, smooth muscle cells or both did not alter the size of neointimal lesions generated by denuding or non-denuding arterial injury.
Conclusion: Neointimal lesion formation following denuding injury to the femoral artery is inhibited by endogenous androgens, independent of the vascular androgen receptor.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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