A sex-specific role for androgens in angiogenesis

Author:

Sieveking Daniel P.12,Lim Patrick1,Chow Renée W.Y.1,Dunn Louise L.1,Bao Shisan2,McGrath Kristine C.Y.1,Heather Alison K.1,Handelsman David J.34,Celermajer David S.125,Ng Martin K.C.125

Affiliation:

1. Heart Research Institute, Sydney 2042, Australia

2. Department of Medicine and Department of Pathology, University of Sydney, Sydney 2050, Australia

3. ANZAC Research Institute, Sydney 2139, Australia

4. Department of Andrology, Concord Hospital, Sydney 2139, Australia

5. Department of Cardiology, Royal Prince Alfred Hospital, Sydney 2050, Australia

Abstract

Mounting evidence suggests that in men, serum levels of testosterone are negatively correlated to cardiovascular and all-cause mortality. We studied the role of androgens in angiogenesis, a process critical in cardiovascular repair/regeneration, in males and females. Androgen exposure augmented key angiogenic events in vitro. Strikingly, this occurred in male but not female endothelial cells (ECs). Androgen receptor (AR) antagonism or gene knockdown abrogated these effects in male ECs. Overexpression of AR in female ECs conferred androgen sensitivity with respect to angiogenesis. In vivo, castration dramatically reduced neovascularization of Matrigel plugs. Androgen treatment fully reversed this effect in male mice but had no effect in female mice. Furthermore, orchidectomy impaired blood-flow recovery from hindlimb ischemia, a finding rescued by androgen treatment. Our findings suggest that endogenous androgens modulate angiogenesis in a sex-dependent manner, with implications for the role of androgen replacement in men.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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