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 language | English (US) |
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Pages (from-to) | 72-80 |
Number of pages | 9 |
Journal | Biochimica et Biophysica Acta - Molecular Basis of Disease |
Volume | 1772 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2007 |
Keywords
- Aging
- Atherosclerosis
- DNA methylation
- Epigenetic dysregulation
- Estrogen receptor beta
- In-vitro senescence
ASJC Scopus subject areas
- Molecular Biology
- Molecular Medicine
- Biophysics