Androgens use different sex hormone receptor pathways to regulate calcification of advanced atherosclerotic lesions depending on the stage of lesion development

Alison K. Heather, Lucinda S. McRobb

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Background: Calcification is an important morphological feature of advanced atherosclerotic
lesions however its regulation in the vasculature is poorly understood. Evidence of higher levels
of calcification in males compared to females suggests hormones may play a role. This study
examined the effect of androgen treatment on calcification of advanced lesions and the
molecular pathways involved. Methods: 34 week old male and female ApoE knockout mice
were treated with testosterone (T) or dihydrotestosterone (DHT) (a non-aromatisable androgen)
for 8 weeks. Plaque and calcified area were quantified in stained sections from the aortic sinus
and innominate artery. Protein expression was examined by immunohistochemistry. Results:
T and DHT treatment modulated the rate of calcification of advanced lesions in a site-specific,
but gender-independent manner. Variable effects of androgens on calcification were independent
of effects on plaque growth or lipid levels but were associated with regulation of sex
hormone receptor expression. In the more advanced lesions of the innominate artery,
calcification was more extensive than in the sinus and both T and DHT treatment increased
calcification. High androgen receptor (AR) expression co-localised with mineralised regions and
osteoblast-like cells suggesting a direct effect of androgens on mineralisation via the AR in this
region. In the less advanced lesions of the aortic sinus, T but not DHT treatment increased
calcification. Calcification was inversely associated with estrogen receptor alpha (ERalpha) but
not AR expression suggesting involvement of the aromatase pathway in T action, consistent
with the divergent effects of T and DHT in this region. Conclusions: Androgens regulate lesion
calcification by divergent pathways depending upon the stage of lesion development. In
advanced lesions, androgens directly regulate mineralisation via up-regulation of AR in
osteoblast-like cells, but in less advanced lesions regulate mineralisation indirectly via ERalpha.
Original languageEnglish
Article numberP461
Pages (from-to)E117-E117
Number of pages1
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes
Event9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology - Atlanta, Gabon
Duration: 16 Apr 200818 Apr 2008

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