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 journalArticlepeer-review

Abstract / Description of output

AIMS: Low androgen levels have been linked with 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 androgen receptor (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 characterised 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 body weight, 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: 2.4x10(7)±4.5x10(6) vs 3.9x10(7)±4.9x10(6) µm(3), 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
Issue number2
Early online date4 Jun 2014
Publication statusPublished - 15 Jul 2014


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