Physiological and pathophysiological actions of androgens in the cardiovascular system

Despite a strong male preponderance in cardiovascular disease, actions of androgens (“male” sex steroids, e.g. testosterone, mainly acting via the androgen receptor; AR) are poorly defined.

Observational and genetic studies as well as studies of androgen deprivation therapy of prostate cancer support that androgens exert clinically significant cardiovascular effects.

We have previously found that both male and female AR knockout mice display increased atherosclerosis and show aberrations in the immune system, which may result in both beneficial and adverse cardiovascular effects.The overall aim of our research is to determine the cardiovascular actions of androgens in both sexes and pinpoint underlying mechanisms.

In a 5-year project, we will 1) Study cardiac phenotypes in mice with unique cell-specific knockouts of the AR; 2) Determine if local “intracrine” production of androgens is an important response to cardiac load; 3) In experimental and registry studies address if and how androgens adversely affect outcomes post myocardial infarction; 4) Measure serum androgens by state-of-the-art liquid chromatography-tandem mass spectrometry and define associations with cardiovascular phenotypes in large population-based cohorts of men and women.Our research may shed light over sex differences in cardiovascular disease, suggest benefits and risks associated with androgen replacement to both sexes, and give basic information for future development of selective AR modulators.