Correlating androgen and estrogen steroid receptor expression with coronary calcification and atherosclerosis in men without known coronary artery disease.
BACKGROUND
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Liu
Peter Y
PY
Division of Endocrinology, Metabolism, Diabetes and Nutrition, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. pliu@labiomed.org
Christian
Rose C
RC
Ruan
Ming
M
Miller
Virginia M
VM
Fitzpatrick
Lorraine A
LA
D000368:Aged; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology; D001344:Autopsy; D002114:Calcinosis / Q000235:genetics / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000235:genetics*; D012044:Regression Analysis; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen