| First Author | Wilhelmson AS | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 7 | Pages | 1519-1527 |
| PubMed ID | 29853568 | Mgi Jnum | J:285158 |
| Mgi Id | MGI:6385472 | Doi | 10.1161/ATVBAHA.118.311252 |
| Citation | Wilhelmson AS, et al. (2018) Testosterone Protects Against Atherosclerosis in Male Mice by Targeting Thymic Epithelial Cells-Brief Report. Arterioscler Thromb Vasc Biol 38(7):1519-1527 |
| abstractText | OBJECTIVE: 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. APPROACH AND RESULTS: 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 infiltration of T cells in the vascular adventitia, supporting a T-cell-driven mechanism. Consistent with a role of the thymus, E-ARKO apoE(-/-) males subjected to prepubertal thymectomy showed no atherosclerosis phenotype. CONCLUSIONS: We show that atherogenesis induced by testosterone/AR deficiency is thymus- and T-cell dependent in male mice and that the thymic epithelial cell is a likely target cell for the antiatherogenic actions of testosterone. These insights may pave the way for new therapeutic strategies for safer endocrine treatment of prostate cancer. |
