A sex-specific role for androgens in angiogenesis

Sieveking, DP; Lim, P; Chow, RWY; Dunn, LL; Bao, S; McGrath, KCY; Heather, AK; Handelsman, DJ; Celermajer, DS; Ng, MKC

A sex-specific role for androgens in angiogenesis

Sieveking, DP Lim, P Chow, RWY Dunn, LL Bao, S McGrath, KCY

Heather, AK Handelsman, DJ Celermajer, DS Ng, MKC

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Publication Type:: Journal Article
Citation:: Journal of Experimental Medicine, 2010, 207 (2), pp. 345 - 352
Issue Date:: 2010-02-15

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Field	Value	Language
dc.contributor.author	Sieveking, DP	en_US
dc.contributor.author	Lim, P	en_US
dc.contributor.author	Chow, RWY	en_US
dc.contributor.author	Dunn, LL	en_US
dc.contributor.author	Bao, S	en_US
dc.contributor.author	McGrath, KCY https://orcid.org/0000-0002-6244-3929	en_US
dc.contributor.author	Heather, AK	en_US
dc.contributor.author	Handelsman, DJ	en_US
dc.contributor.author	Celermajer, DS	en_US
dc.contributor.author	Ng, MKC	en_US
dc.date.issued	2010-02-15	en_US
dc.identifier.citation	Journal of Experimental Medicine, 2010, 207 (2), pp. 345 - 352	en_US
dc.identifier.issn	0022-1007	en_US
dc.identifier.uri	http://hdl.handle.net/10453/17047
dc.description.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. © 2010 Sieveking et al.	en_US
dc.relation.ispartof	Journal of Experimental Medicine	en_US
dc.relation.isbasedon	10.1084/jem.20091924	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Hindlimb	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Cardiovascular Diseases	en_US
dc.subject.mesh	Ischemia	en_US
dc.subject.mesh	Neovascularization, Pathologic	en_US
dc.subject.mesh	Dihydrotestosterone	en_US
dc.subject.mesh	Receptors, Androgen	en_US
dc.subject.mesh	Castration	en_US
dc.subject.mesh	Sex Factors	en_US
dc.subject.mesh	Recovery of Function	en_US
dc.subject.mesh	Neovascularization, Physiologic	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Androgen Receptor Antagonists	en_US
dc.title	A sex-specific role for androgens in angiogenesis	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	207	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	11 Medical and Health Sciences	en_US
dc.location.activity	ISI:000274493900011	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	207	en_US

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. © 2010 Sieveking et al.

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http://hdl.handle.net/10453/17047