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Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification.

Zhu D, Hadoke PW, Wu J, Vesey AT, Lerman DA, Dweck MR, Newby DE, Smith LB, MacRae VE - Sci Rep (2016)

Bottom Line: 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.Androgen signalling may represent a novel potential therapeutic target for clinical intervention.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.

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.

No MeSH data available.


Related in: MedlinePlus

Testosterone has no effect on apoptosis of VSMCs.Testosterone or DHT (100 nM) treatment does not (a) reduce VSMC viability (n = 6) or (b) induce apoptosis (n = 6).
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f5: Testosterone has no effect on apoptosis of VSMCs.Testosterone or DHT (100 nM) treatment does not (a) reduce VSMC viability (n = 6) or (b) induce apoptosis (n = 6).

Mentions: Apoptosis plays an important role in vascular calcification, we therefore examined the effect of testosterone treatment on VSMC apoptosis. Alamar blue assay showed no effect of either testosterone or DHT on cell viability (Fig. 5a). DAPI staining revealed no effect of either testosterone or DHT on nuclei apoptosis (Fig. 5b).


Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification.

Zhu D, Hadoke PW, Wu J, Vesey AT, Lerman DA, Dweck MR, Newby DE, Smith LB, MacRae VE - Sci Rep (2016)

Testosterone has no effect on apoptosis of VSMCs.Testosterone or DHT (100 nM) treatment does not (a) reduce VSMC viability (n = 6) or (b) induce apoptosis (n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837411&req=5

f5: Testosterone has no effect on apoptosis of VSMCs.Testosterone or DHT (100 nM) treatment does not (a) reduce VSMC viability (n = 6) or (b) induce apoptosis (n = 6).
Mentions: Apoptosis plays an important role in vascular calcification, we therefore examined the effect of testosterone treatment on VSMC apoptosis. Alamar blue assay showed no effect of either testosterone or DHT on cell viability (Fig. 5a). DAPI staining revealed no effect of either testosterone or DHT on nuclei apoptosis (Fig. 5b).

Bottom Line: 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.Androgen signalling may represent a novel potential therapeutic target for clinical intervention.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.

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.

No MeSH data available.


Related in: MedlinePlus