The Role of Testosterone in Atherosclerosis: View From Cell Cultures and Animal Models

Testosterone (TES) has complex roles in cardiovascular disease, influencing not only atherosclerosis development in general, but also atherosclerosis-related processes associated with hypertension, cholesterol metabolism, vascular calcification, and arterial stiffness. This review examines TES's effects, particularly its atheroprotective role in various mice and minipig model systems and cell cultures. TES modulates the renin-angiotensin system (RAS), contributing to hypertension and vascular dysfunction, but its deprivation can mitigate these effects. TES also impacts cholesterol metabolism by regulating liver X receptor (LXRα) pathways, promoting both cholesterol clearance and synthesis. Moreover, TES is involved in vascular calcification via androgen receptor (AR) signalling, a process that contributes to arterial stiffness, especially in females. The review highlights gaps in understanding TES's specific molecular mechanisms in cardiovascular disease, emphasising the need for further research to explore sex-specific responses and potential therapeutic interventions.