(Circulation. 1999;99:2317-2322.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Androgen Exposure Increases Human Monocyte Adhesion to Vascular Endothelium and Endothelial Cell Expression of Vascular Cell Adhesion Molecule-1
From the Heart Research Institute (J.A.M., W.J., D.S.C.); the Departments of Cardiology (J.A.M., D.S.C.) and Andrology (D.J.H.), Royal Prince Alfred Hospital; and the Department of Medicine, Sydney University (D.J.H., D.S.C.), Sydney, Australia.
Correspondence to Dr Jane A. McCrohon, Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown 2050, Sydney, Australia. E-mail janem{at}card.rpa.cs.nsw.gov.au
Background—Male sex is an independent risk factor for coronary artery disease. Owing to the importance of monocyte adhesion to endothelial cells in the development of atherosclerosis, we hypothesized that androgens might promote this process. We therefore studied the effects of the nonaromatizable androgen dihydrotestosterone (DHT) on human monocyte adhesion to human endothelial cells and on endothelial cell–surface expression of adhesion molecules.
Methods and Results—Human umbilical vein
endothelial cells (HUVECs) were grown to confluence in
media supplemented with postmenopausal female serum, then exposed for
48 hours to either DHT (40 and 400 nmol/L), with or without the
androgen receptor blocker hydroxyflutamide (HF) (4 µmol/L); HF
alone; or vehicle control (ethanol 0.1%). Human monocytes obtained by
elutriation were incubated for 1 hour with the HUVECs at 37°C, and
adhesion was measured by light microscopy. Compared with vehicle
control, monocyte adhesion was increased in the androgen-treated HUVECs
in a dose-dependent manner (116±6% and 128±3% for DHT 40 and 400
nmol/L respectively; P<0.001). HF blocked this increase
(P
0.3 compared with control). Surface expression of
endothelial cell adhesion molecules was measured by
ELISA and revealed an increased expression of vascular cell adhesion
molecule-1 (VCAM-1) in the DHT-treated HUVECs (125±5% versus 100±4%
in controls; P=0.002), an effect also antagonized by HF
(P0.3 compared with controls). Furthermore, the
DHT-related increase in adhesion was completely blocked by coincubation
with anti–VCAM-1 antibody. Comparable results were obtained in
arterial endothelial cells and in
endothelium stimulated with the cytokine tumor
necrosis factor-
.
Conclusions—Androgen exposure is associated with increased human monocyte adhesion to endothelial cells, a proatherogenic effect mediated at least in part by an increased endothelial cell–surface expression of VCAM-1.
Key Words: hormones • atherosclerosis • cell adhesion molecules
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