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Cardiovascular Research 1999 43(4):985-991; doi:10.1016/S0008-6363(99)00153-4
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system

Wendy S Posta,*, Pascal J Goldschmidt-Clermonta,b,e, Calvin C Wilhidea,b, Alan W Heldmana, Mark S Sussmanc, Pamela Ouyanga, Emily E Millikena and Jean-Pierre J Issad

aDepartment of Medicine, Carnegie 568-Cardiology Division, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
bDepartment of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
cDepartment of Surgery, Cardiovascular Division, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
dOncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
eHeart and Lung Institute, The Ohio State University, Columbus, OH, USA

* Corresponding author. Tel.: +1-410-955-7376; fax: +1-410-614-1685 wpost{at}jhmi.edu

Objective: Methylation of the promoter region of the estrogen receptor gene alpha (ER {alpha}) occurs as a function of age in human colon, and results in inactivation of gene transcription. In this study, we sought to determine whether such age-related methylation occurs in the cardiovascular system, and whether it is associated with atherosclerotic disease. Methods: We used Southern blot analysis to determine the methylation state of the ER {alpha} gene in human right atrium, aorta, internal mammary artery, saphenous vein, coronary atherectomy samples, as well as cultured aortic endothelial cells and smooth muscle cells. Results: An age related increase in ER {alpha} gene methylation occurs in the right atrium (range 6 to 19%, R=0.36, P<0.05). Significant levels of ER {alpha} methylation were detected in both veins and arteries. In addition, ER {alpha} gene methylation appears to be increased in coronary atherosclerotic plaques when compared to normal proximal aorta (10±2% versus 4±1%, P<0.01). In endothelial cells explanted from human aorta and grown in vitro, ER {alpha} gene methylation remains low. In contrast, cultured aortic smooth muscle cells contain a high level of ER {alpha} gene methylation (19–99%). Conclusions: Methylation associated inactivation of the ER {alpha} gene in vascular tissue may play a role in atherogenesis and aging of the vascular system. This potentially reversible defect may provide a new target for intervention in heart disease.

KEYWORDS DNA methylation; Receptors; Atherosclerosis; Aging; Hormones


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