Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence.
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 beta 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 beta 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 beta methylation was observed in three of six human aortic endothelial or smooth muscle cell lines cultured in-vitro to vascular senescence. Estrogen receptor beta 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 beta in atherosclerosis and vascular aging. We suggest that focal epigenetic changes in estrogen receptor beta contribute to the development of atherosclerosis and vascular aging.
Kim
Jei
J
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. jeikim@cnu.ac.kr
Kim
Jee Yeon
JY
Song
Kyu Sang
KS
Lee
Young Ho
YH
Seo
Joong Seok
JS
Jelinek
Jaroslav
J
Goldschmidt-Clermont
Pascal J
PJ
Issa
Jean-Pierre J
JP
D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic
D004791:Enzyme Inhibitors; D047629:Estrogen Receptor beta