Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification
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Hadoke, Patrick WF
Wu, Junxi
Vesey, Alex T
Lerman, Daniel A
Dweck, Marc R
Newby, David E
Smith, Lee B
MacRae, Vicky E
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Abstract
Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention.
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Scientific Reports
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6
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1
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© The Authors 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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Cardiovascular medicine and haematology
Biomedical and clinical sciences
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CORONARY-ARTERY CALCIFICATION
SERUM TESTOSTERONE
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Zhu, D; Hadoke, PWF; Wu, J; Vesey, AT; Lerman, DA; Dweck, MR; Newby, DE; Smith, LB; MacRae, VE, Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification, Scientific Reports, 2016, 6 (1), pp. 24807