Dehydroepiandrosterone, an adrenalandrogen, increases human foam cell formation
a potentially pro-atherogenic effect
Martin K. C. Ng, MBBS, FRACP* ,
Shirley Nakhla, BSc,
Anna Baoutina, PhD ,
Wendy Jessup, PhD,
David J. Handelsman, MBBS, PhD, FRACP || and
David S. Celermajer, MBBS, PhD, FRACP*,*
* Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
Heart Research Institute, Sydney, Australia
Centre for Vascular Research, University of New South Wales, Sydney, Australia
Department of Andrology, Concord Hospital, Sydney, Australia
|| ANZAC Research Institute, Sydney, Australia
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Figure 1 Monocyte adhesion to endothelium (in the basal or interleukin-1-beta [IL-1-beta]–stimulated state) for each treatment condition, expressed as a percentage of control values. Dehydroepiandrosterone (DHEA) (in young adults and at supraphysiologic concentrations) had no significant effect on monocyte adhesion to endothelium (p = 0.56 by analysis of variance [ANOVA] for adhesion in either the basal or IL-1-beta–stimulated state).
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Figure 2 Endothelial cell-surface expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin for each treatment group in the basal (A) and IL-1-beta–stimulated (B) states. Results are expressed as a percentage of control values. DHEA had no significant effect on endothelial cell-surface expression of VCAM-1, ICAM-1, or E-selectin (p > 0.1 by ANOVA for each cell adhesion molecule [CAM] in each treatment group). Abbreviations as in Figure 1.
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Figure 3 Exposure to DHEA was associated with a dose-dependent increase in cholesteryl ester (CE) accumulation in human macrophages from male donors, over the physiologic range (4.2 to 42 nmol/l). This effect is abrogated by co-incubation with the androgen receptor antagonist HF. *p = 0.015 by ANOVA. There was a polynomial relationship between the DHEA concentration and macrophage CE content (r = 0.997). Abbreviations as in Figure 1.
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Figure 4 Effects of dehydroepiandrosterone (DHEA) exposure on macrophage gene expression. (A) Gene expression examined by reverse-transcription polymerase chain reaction shows that DHEA at physiologic concentrations upregulates the lipoprotein-processing genes acyl coenzyme A:cholesterol acyltransferase I (ACAT) and lysosomal acid lipase (LAL). (B) In contrast, DHEA exposure had no significant effect on expression of the scavenger receptors A1 and A2. *p < 0.05 versus control values for ACAT and LAL (vs. p > 0.2 for scavenger receptors A1 and 2). Open columns = control; shaded columns = DHEA at 42 nmol/l.
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