Modulation of neointimal lesion formation by endogenous androgens is independent of vascular androgen receptor

Junxi Wu, Patrick W.F. Hadoke, Iris Mair, Win Gel Lim, Eileen Miller, Martin A. Denvir, Lee B. Smith

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Aims Lowandrogen levels have been linked with an increased risk of cardiovascular disease in men. Previous studies have suggested that androgens directly inhibit atherosclerotic lesion formation although the underlying mechanisms for this remain unclear. This study addressed the hypothesis that endogenous androgens inhibit arterial remodelling by a direct action on the androgen receptor (AR) in the vascular wall. Methods and results We studied a series of novel mouse lines with cell-specific deletion of the AR in either the endothelium or in smooth muscle cells or both cell types. Findings were compared with a model of global androgen deficiency in wild-type mice (castrated).We characterized the cardiovascular phenotype, vascular pharmacology and histology, and assessed neointimal lesion formation following vascular injury to the femoral artery. Cell-specific AR deletion did not alter bodyweight, circulating testosterone levels or seminal vesicle weight, but caused limited alterations in arterial contractility and blood pressure. Neointimal lesion formation was unaltered by selective deletion of AR from the vascular endothelium, smooth muscle, or both cell types. Castration in wild-type mice increased neointimal lesion volume (Sham vs. Castration: 2.4 × 107+4.5 × 106 vs. 3.9 × 107+4.9 × 106 mm3, P ± 0.04, n ± 9-10). Conclusion Vascular cell-specific AR deletion had no effect on neointimal lesion formation, while low systemic androgen levels adversely affect neointimal lesion size. These findings suggest that the cardio-protective effects of androgens are mediated either by AR outside the vasculature or by AR-independent mechanisms.

Original languageEnglish
Pages (from-to)281-290
Number of pages10
JournalCardiovascular Research
Volume103
Issue number2
DOIs
Publication statusPublished - 15 Jul 2014

Keywords

  • androgen receptor
  • arterial injury
  • neointima
  • testosterone

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