Unknown

Dataset Information

0

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


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.

SUBMITTER: Zhu D 

PROVIDER: S-EPMC4837411 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Zhu Dongxing D   Hadoke Patrick W F PW   Wu Junxi J   Vesey Alex T AT   Lerman Daniel A DA   Dweck Marc R MR   Newby David E DE   Smith Lee B LB   MacRae Vicky E VE  

Scientific reports 20160420


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 t  ...[more]

Similar Datasets

| S-EPMC4406354 | biostudies-literature
| S-EPMC6642823 | biostudies-literature
| S-EPMC4369260 | biostudies-literature
| S-EPMC6458154 | biostudies-literature
| S-EPMC3678289 | biostudies-literature
| S-EPMC3129914 | biostudies-literature
| S-EPMC6909180 | biostudies-literature
| S-EPMC3562655 | biostudies-literature