Testosterone and cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death in Sweden and globally. Atherosclerosis is the most important underlying mechanism for ischemic heart disease, the major form of CVD. A smaller, but clinically important, type of CVD is abdominal aortic aneurysms (AAAs).

An AAA is a pathological widening of the abdominal aorta, which in many cases remains asymptomatic but may result in a life-threatening sudden rupture of the aortic wall. Although certain risk factors are shared between atherosclerotic cardiovascular disease and AAAs, these clearly represent two distinct vascular diseases.

Since a few years back, all Swedish men, but not women, are offered an ultrasound screening for AAA at 65 years of age. There is a strong male preponderance in both atherosclerosis-based CVD and AAAs, but the actions of sex steroids in these diseases are poorly defined.

The overall aim of our research is to determine the role of androgens (“male” sex steroids, e.g. testosterone) in atherosclerotic CVD and AAAs, with a particular focus on immunological mediators. In our research, we combine epidemiology with studies in genetically manipulated mice to answer questions concerning the cardiovascular actions of sex steroids.

Key publications

Low Progesterone and Low Estradiol Levels Associate With Abdominal Aortic Aneurysms in Men.
Ohlsson C, Langenskiöld M, Smidfelt K, Poutanen M, Ryberg H, Norlén AK, Nordanstig J, Bergström G, Tivesten Å. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1413-e1425. doi: 10.1210/clinem/dgab867. PMID: 34865072 Free PMC article.

Testosterone reduces metabolic brown fat activity in male mice.
Lantero Rodriguez M, Schilperoort M, Johansson I, Svedlund Eriksson E, Palsdottir V, Kroon J, Henricsson M, Kooijman S, Ericson M, Borén J, Ohlsson C, Jansson JO, Levin MC, Rensen PCN, Tivesten Å. J Endocrinol. 2021 Sep 3;251(1):83-96. doi: 10.1530/JOE-20-0263. PMID: 34370693

Wilhelmson AS, Lantero Rodriguez M, Stubelius A, Fogelstrand P, Johansson I, Buechler MB, Lianoglou S, Kapoor VN, Johansson ME, Fagman JB, Duhlin A, Tripathi P, Camponeschi A, Porse BT, Rolink AG, Nissbrandt H, Turley SJ, Carlsten H, Mårtensson IL, Karlsson MCI, Tivesten Å.
Testosterone is an endogenous regulator of BAFF and splenic B cell number. 
Nature Communications 2018 May 25;9(1):2067.

Wilhelmson AS, Lantero Rodriguez M, Svedlund Eriksson E, Johansson I, Fogelstrand P, Stubelius A, Lindgren S, Fagman JB, Hansson GK, Carlsten H, Karlsson MCI, Ekwall O, Tivesten Å.
Testosterone protects against atherosclerosis in male mice by targeting thymic epithelial cells.
Arteriosclerosis, Thrombosis, and Vascular Biology 2018 Jul;38(7):1519-1527.

Wilhelmson AS, Fagman JB, Johansson I, Zou ZV, Andersson AG, Svedlund Eriksson E, Johansson ME, Lindahl P, Fogelstrand P, Tivesten Å.
Increased Intimal Hyperplasia After Vascular Injury in Male Androgen Receptor-Deficient Mice.
Endocrinology. 157(10):3915-3923. Epub 2016 Aug 17. (2016)

Fagman JB, Wilhelmson AS, Motta BM, Pirazzi C, Alexanderson C, De Gendt K, Verhoeven G, Holmäng A, Anesten F, Jansson JO, Levin M, Borén J, Ohlsson C, Krettek A, Romeo S, Tivesten Å.
The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice.
FASEB J. 29(4):1540-50. (2015)

Tivesten Å, Nilsson M, Carlzon D, Vandenput L, Karlsson MK, Ljunggren Ö, Barrett-Connor E, Mellström D, Ohlsson C.
Dehydroepiandrosterone and its sulfate predict the 5-year risk of coronary heart disease events in elderly men.
J Am Coll Cardiol. 64(17):1801-10. (2014)

Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellström D, Tivesten Å.
High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden.
J Am Coll of Cardiol. 58(16):1674-81. (2011)

Leukocyte subsets and abdominal aortic aneurysms detected by screening in men.
Langenskiöld M, Smidfelt K, Nordanstig J, Bergström G, Tivesten Å. J Intern Med. 2020 Mar 15. doi: 10.1111/joim.13040. Online ahead of print. PMID: 32173961

Original Research ARTICLE
Androgen Receptors in Epithelial Cells Regulate Thymopoiesis and Recent Thymic Emigrants in Male Mice
Anna S. Wilhelmson1†, Marta Lantero Rodriguez1, Inger Johansson1, Elin Svedlund Eriksson1, Alexandra Stubelius2,3†, Susanne Lindgren3,4, Johan Bourghardt Fagman1†, Pamela J. Fink5, Hans Carlsten2,3, Olov Ekwall3,4 and Åsa Tivesten1*‡
Front. Immunol., 29 June 2020 | https://doi.org/10.3389/fimmu.2020.01342