Correlating Androgen and Estrogen Steroid Receptor Expression with Coronary Calcification and Atherosclerosis in Men without Known Coronary Artery Disease

Abstract

Accumulating data emphasize the gender specificity of key components of the atherosclerotic process and the importance of gonadal steroids on the human vasculature. Steroid receptors, including the androgen receptor (AR) and estrogen receptors (ERs) alpha and beta are expressed in key vascular tissues, including endothelial cells and vascular smooth muscle cells. However, the relative abundance and importance of these receptors in the coronary artery are not well defined, particularly in men. We therefore examined AR, ER alpha, and ER beta expression as a function of key components of atherosclerosis, namely plaque and calcium area, in male human coronary arteries. Coronary arteries were obtained at autopsy from 24 men without known coronary artery disease. Coronary calcification was measured by contact microradiography, and atherosclerotic plaque area was quantified histologically. Coronary artery cross-sections were immunostained for AR, ER alpha, and ER beta and then measured semiquantitatively in each arterial wall layer (intima, adventitia, and media). AR, ER beta, and ER alpha were expressed in all artery wall layers but most avidly in the media (P < 0.001). ER beta exceeded ER alpha expression (P < 0.0005). AR expression in the media correlated negatively with plaque area (P = 0.006, R = -0.55), whereas intimal ER beta expression correlated positively with plaque area (P = 0.012, R = 0.50). We conclude that both AR and ER beta are important in relatively early coronary atherosclerosis, but inversely so, because decreasing AR and increasing ER beta expression correlate with more extensive atherosclerosis. ER beta seems to be the predominate ER in coronary arteries harvested from men without known coronary artery disease. Interventional studies are required to assess the functional significance of these observations.