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

Wendy S. Post, Pascal J. Goldschmidt-Clermont, Calvin C. Wilhide, Alan W. Heldman, Mark S. Sussman, Pamela Ouyang, Emily E. Milliken, Jean Pierre J. Issa

Research output: Contribution to journalArticlepeer-review


Objective: Methylation of the promoter region of the estrogen receptor gene alpha (ER α) 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 α 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 α gene methylation occurs in the right atrium (range 6 to 19%, R=0.36, P<0.05). Significant levels of ER α methylation were detected in both veins and arteries. In addition, ER α 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 α gene methylation remains low. In contrast, cultured aortic smooth muscle cells contain a high level of ER α gene methylation (19-99%). Conclusions: Methylation associated inactivation of the ER α 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. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
JournalCardiovascular research
Issue number4
StatePublished - Sep 1999


  • Aging
  • Atherosclerosis
  • DNA methylation
  • Hormones
  • Receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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