Epigenetic changes in estrogen receptor β gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence

Jei Kim, Jee Yeon Kim, Kyu Sang Song, Young Ho Lee, Joong Seok Seo, Jaroslav Jelinek, Pascal J. Goldschmidt-Clermont, Jean Pierre J. Issa

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Epigenetic changes marked by DNA methylation have been proposed to play a role in age-related disease. We investigated DNA methylation changes in cardiovascular atherosclerotic tissues and in-vitro vascular senescence in the promoter of estrogen receptor β gene, which has essential roles in vascular function. Coronary atherosclerotic tissues showed higher methylation levels (28.7%) than normal appearing arterial (6.7%-10.1%) and venous tissues (18.2%). In comparing estrogen receptor β methylation between plaque and non-plaque regions in ascending aorta, common carotid artery, and femoral artery of two patients, the plaque lesions showed consistently higher methylation levels than non-plaque regions. Passage-dependent increased estrogen receptor β methylation was observed in three of six human aortic endothelial or smooth muscle cell lines cultured in-vitro to vascular senescence. Estrogen receptor β expression in these vascular cell lines was significantly activated by DNA-methyltransferase inhibition. This activity was augmented by histone deacetylase inhibition. These findings provide evidence of epigenetic dysregulation of estrogen receptor β in atherosclerosis and vascular aging. We suggest that focal epigenetic changes in estrogen receptor β contribute to the development of atherosclerosis and vascular aging.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1772
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Aging
  • Atherosclerosis
  • DNA methylation
  • Epigenetic dysregulation
  • Estrogen receptor beta
  • In-vitro senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

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