Testosterone Protects Against Atherosclerosis in Male Mice by Targeting Thymic Epithelial Cells-Brief Report

Arteriosclerosis, Thrombosis, and Vascular Biology
Anna S WilhelmsonÅsa Tivesten

Abstract

Androgen deprivation therapy has been associated with increased cardiovascular risk in men. Experimental studies support that testosterone protects against atherosclerosis, but the target cell remains unclear. T cells are important modulators of atherosclerosis, and deficiency of testosterone or its receptor, the AR (androgen receptor), induces a prominent increase in thymus size. Here, we tested the hypothesis that atherosclerosis induced by testosterone deficiency in male mice is T-cell dependent. Further, given the important role of the thymic epithelium for T-cell homeostasis and development, we hypothesized that depletion of the AR in thymic epithelial cells will result in increased atherosclerosis. Prepubertal castration of male atherosclerosis-prone apoE-/- mice increased atherosclerotic lesion area. Depletion of T cells using an anti-CD3 antibody abolished castration-induced atherogenesis, demonstrating a role of T cells. Male mice with depletion of the AR specifically in epithelial cells (E-ARKO [epithelial cell-specific AR knockout] mice) showed increased thymus weight, comparable with that of castrated mice. E-ARKO mice on an apoE-/- background displayed significantly increased atherosclerosis and increased infiltrat...Continue Reading

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Citations

Apr 25, 2019·The Journal of Endocrinology·Bo-Kyung SonMasahiro Akishita
Dec 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Jul 16, 2020·International Journal of Molecular Sciences·Amela Jusic On Behalf Of The Eu-CardioRNA Cost Action
Jul 28, 2020·Frontiers in Immunology·Anna S WilhelmsonÅsa Tivesten
Mar 28, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Congqing WuHong S Lu
Apr 28, 2021·Biochemical and Biophysical Research Communications·Kentaro AonoAtsushi Yamauchi

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Methods Mentioned

BETA
Flow
flow cytometry
FACS

Software Mentioned

GraphPad
Prism
BioPix
FlowJo Star

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