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The role of androgen receptors in atherosclerosis
Kaloyan Takov1, Junxi Wu2, Martin A Denvir1
1University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
Insights
Androgens, like testosterone, may protect against atherosclerosis, a key cause of cardiovascular events. Further research into androgen receptors (AR) is needed to clarify their role and potential therapeutic applications.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Molecular Biology
Background:
- Men exhibit a recognized disadvantage in cardiovascular health.
- The specific impact of androgens on atherosclerosis, a primary contributor to severe cardiovascular events, remains incompletely understood.
- Increased clinical use of testosterone necessitates understanding its cardiovascular side effects, particularly concerning androgen supplementation and deprivation therapies.
Purpose of the Study:
- To investigate the complex role of androgens and androgen receptors (AR) in the development of atherosclerosis.
- To explore potential atheroprotective mechanisms of testosterone, including conversion to estradiol and direct AR activation.
- To highlight the utility of cell-specific AR knockout animal models in elucidating androgen action in atherosclerosis.
Main Methods:
- Review of existing literature on androgens, testosterone, and atherosclerosis.
- Analysis of studies utilizing cell-specific androgen receptor (AR) knockout animal models.
- Examination of potential atheroprotective pathways mediated by testosterone and its metabolites.
Main Results:
- Evidence suggests androgens may possess atheroprotective properties.
- The precise role of the androgen receptor (AR) in atherogenesis is complex and not fully elucidated.
- Cell-specific AR knockout models are crucial for dissecting the nuanced functions of AR in atherosclerosis.
Conclusions:
- Androgen action in atherosclerosis is intricate, with the exact role of the androgen receptor (AR) requiring further clarification.
- Continued investigation using AR knockout models is essential for understanding AR's function in atherogenesis.
- Elucidating the role of AR may unlock new therapeutic targets for cardiovascular disease prevention and treatment.
Abstract:
Male disadvantage in cardiovascular health is well recognised. However, the influence of androgens on atherosclerosis, one of the major causes of many life-threatening cardiovascular events, is not well understood. With the dramatic increase in clinical prescription of testosterone in the past decade, concerns about the cardiovascular side-effects of androgen supplementation or androgen deprivation therapy are increasing. Potential atheroprotective effects of testosterone could be secondary to (aromatase-mediated) conversion into oestradiol or, alternatively, to direct activation of androgen receptors (AR). Recent development of animal models with cell-specific AR knockout has indicated a complex role for androgen action in atherosclerosis. Most studies suggest androgens are atheroprotective but the precise role of AR remains unclear. Increased use of AR knockout models should clarify the role of AR in atherogenesis and, thus, lead to exploitation of this pathway as a therapeutic target.