TY - JOUR
T1 - Estrogen receptors in atherosclerotic human aorta
T2 - Inhibition of human vascular smooth muscle cell proliferation by estrogens
AU - Nakamura, Yasuhiro
AU - Suzuki, Takashi
AU - Miki, Yasuhiro
AU - Tazawa, Chika
AU - Senzaki, Kumiko
AU - Moriya, Takuya
AU - Saito, Haruo
AU - Ishibashi, Tadashi
AU - Takahashi, Syouki
AU - Yamada, Shogo
AU - Sasano, Hironobu
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/4/30
Y1 - 2004/4/30
N2 - Estrogen has been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). Therefore, we believe it is important to examine the status of ER expression in the human cardiovascular system and its disorders. In this study, we first evaluated the relative abundance of messenger RNA (mRNA) of both ER subtypes (ERα and ERβ) in the human aorta using reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR). We then examined the immunolocalization of both ERs in VSMCs of human atherosclerotic lesions. In order to examine which ER subtype was associated with the anti-atherogenic effects of estrogen, we examined the effects of estrogen in two VSMC cell lines, one positive only for ERα and the other positive only for ERβ. The relative abundance of mRNAs for both ERs was higher in female aorta with a mild degree of atherosclerosis than in female aorta with a severe degree of atherosclerosis (P<0.05). In addition, the number of ERα and/or ERβ double positive cells in the neointima was higher in female aorta with a mild degree of atherosclerosis than in female aorta with severe atherosclerosis (P<0.05). Our in vitro study found that estradiol was able to significantly inhibit the proliferation of ERα positive VSMCs but not ERβ positive VSMCs (P<0.05). Moreover, estradiol was found to significantly suppress proliferating cell nuclear antigen (PCNA) mRNA levels in ERα positive VSMCs compared to that of ERβ positive VSMCs, consistent with the findings of cell proliferation. Results from this study suggest that estrogens can inhibit the proliferation of VSMCs through ERα, especially in pre-menopausal women. Our study also indicates that decreased levels of ER, especially ERα, in the female atherosclerotic neointima may be associated with progression of atherosclerotic changes.
AB - Estrogen has been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). Therefore, we believe it is important to examine the status of ER expression in the human cardiovascular system and its disorders. In this study, we first evaluated the relative abundance of messenger RNA (mRNA) of both ER subtypes (ERα and ERβ) in the human aorta using reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR). We then examined the immunolocalization of both ERs in VSMCs of human atherosclerotic lesions. In order to examine which ER subtype was associated with the anti-atherogenic effects of estrogen, we examined the effects of estrogen in two VSMC cell lines, one positive only for ERα and the other positive only for ERβ. The relative abundance of mRNAs for both ERs was higher in female aorta with a mild degree of atherosclerosis than in female aorta with a severe degree of atherosclerosis (P<0.05). In addition, the number of ERα and/or ERβ double positive cells in the neointima was higher in female aorta with a mild degree of atherosclerosis than in female aorta with severe atherosclerosis (P<0.05). Our in vitro study found that estradiol was able to significantly inhibit the proliferation of ERα positive VSMCs but not ERβ positive VSMCs (P<0.05). Moreover, estradiol was found to significantly suppress proliferating cell nuclear antigen (PCNA) mRNA levels in ERα positive VSMCs compared to that of ERβ positive VSMCs, consistent with the findings of cell proliferation. Results from this study suggest that estrogens can inhibit the proliferation of VSMCs through ERα, especially in pre-menopausal women. Our study also indicates that decreased levels of ER, especially ERα, in the female atherosclerotic neointima may be associated with progression of atherosclerotic changes.
KW - Atherosclerosis
KW - Estrogen receptor
KW - Vascular smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=2442710388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2442710388&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2004.02.013
DO - 10.1016/j.mce.2004.02.013
M3 - Article
C2 - 15149723
AN - SCOPUS:2442710388
VL - 219
SP - 17
EP - 26
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -