TY - JOUR
T1 - Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system
AU - Post, Wendy S.
AU - Goldschmidt-Clermont, Pascal J.
AU - Wilhide, Calvin C.
AU - Heldman, Alan W.
AU - Sussman, Mark S.
AU - Ouyang, Pamela
AU - Milliken, Emily E.
AU - Issa, Jean Pierre J.
N1 - Funding Information:
We thank Dr. Stephen Baylin for reviewing the manuscript and for helpful discussions. JPI is a Kimmel Foundation Scholar. PJG-C is the recipient of an Established Investigator Award from the American Heart Association, and was also supported by NIH grant HL52315, and by the Bernard Foundation.
PY - 1999/9
Y1 - 1999/9
N2 - 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.
AB - 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.
KW - Aging
KW - Atherosclerosis
KW - DNA methylation
KW - Hormones
KW - Receptors
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U2 - 10.1016/S0008-6363(99)00153-4
DO - 10.1016/S0008-6363(99)00153-4
M3 - Article
C2 - 10615426
AN - SCOPUS:0032831285
SN - 0008-6363
VL - 43
SP - 985
EP - 991
JO - Cardiovascular research
JF - Cardiovascular research
IS - 4
ER -