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2001 Fiscal Year Final Research Report Summary

Investigation and clinical application of estrogen receptor α and β prevent vascular disease

Research Project

Project/Area Number 11470157
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

OUCHI Yasuyoshi  Department of Geriatric Medicine, The University of Tokyo, Professor, 医学部・附属病院, 教授 (80168864)

Co-Investigator(Kenkyū-buntansha) KOZAKI Koichi  Department of Geriatric Medicine, The University of Tokyo, Assistant, 医学部・附属病院, 助手 (80272540)
INOUE Satoshi  Department of Geriatric Medicine, The University of Tokyo, Senior Assistant, 医学部・附属病院, 講師 (40251251)
YOSHIZUMI Masao  Department of Geriatric Medicine, The University of Tokyo, Senior Assistant, 医学部・附属病院, 講師 (20282626)
IIJIMA Katsuya  Department of Geriatric Medicine, The University of Tokyo, Assistant, 医学部・附属病院, 助手 (00334384)
Project Period (FY) 1999 – 2001
Keywordsestrogen receptor / vascular smooth muscle cells / adeno virus vector / DNA chip
Research Abstract

The goal of our study is to elucidate the atheroprotective effects of estrogen, especially the role of estrogen receptor (ER) subtype, and to apply a new therapeutic method using ER to prevent atherosclerosis. We have gained six results for the three years, described below. (1) We examined the influence of diabetes mellitus on atherosclerosis in relation to ER. We showed that the expression of Erα was decreased in high glucose state in cultured vascular smooth muscle cells, mediated through the activation of protein kinase C. (2) We successfully constructed transgenic mouse overexpressing mutant ER which has a dominant negative transcriptional activity to both Erα and Erβ. Neointima was formed in this mouse by placing polyethylene cuff around the femoral artery. By this method, we were able to clarify the biophysical effect of ER. (3) We examined which ER subtype was involved in the inhibitory effect of estrogen on vascular smooth muscle cell proliferation using adenovirus-mediated overexpression of Erα and β. We found that the inhibitory effect was mediated mainly via Erβ. (4) Apoptosis of vascular endothelium is supposed to be related to the initiation of atherosclerotic lesion. We showed that estrogen attenuated apoptosis of endothelium. This effect was mediated, in part, through the downregulation of Bax expression. (5) Obesity is one of the important risk factors for atherosclerosis, and estrogen has anti-obese effect. We found that the mechanism of the inhibitory effect of estrogen is through Erβ expressed in the central nervous system. (6) We investigated the association between the polymorphism of CA (cytosine-adenine) repeat in the upstream of Erβ gene and blood pressure in 187 Japanese postmenopausal women. We found that a group of subjects who bears a specific CA repeats showed significant systolic hypertension.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Hashimoto M, Ouchi Y(他6名): "Effects of long-term and reduced-dose hormone replacement therapy on endothelial function and intima-media thickness in postmenopausal women"Menopause. 9(1). 58-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sudoh N, Ouchi Y(他12名): "Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats"Circulation. 103(5). 724-729 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto M, Ouchi Y(他10名): "Effect of acute intake of red wine on flow-mediated vasodilatation of the brachial artery"Am J Cardiol. 88(12). 1457-1460 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa S, Ouchi Y(他11名): "Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor a and b pathways"J Biol Chem. 275(28). 21372-21379 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Liang YQ, Ouchi Y(他10名): "Estrogen attenuates ovariectomy-induced body weight gain through estrogen receptor beta--in the cebtral nervous system"Circulation. 102(suppl). II-349 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto M, Ouchi Y(他8名): "Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men"Arterioscler Thromb Vasc Biol. 19(11). 2795-2800 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大内尉義 編: "高齢女性の健康増進のためのホルモン補充療法ガイドライン"メディカルレビュー社・東京. 308 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashimoto M, Miyao M, Akishita M, Hosoi T, Toba K, Kozaki K, Yoshizumi M, Ouchi Y: "Effects of long-term and reduced-dose hormone replacement therapy on endothelial function and intimamedia thickness in postmenopausal women"Menopause. 9(1). 58-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto M, Kim S, Eto M, Iijima K, Ako J, Yoshizumi M, Akishita M, Kondo K, Itakura H, Hosoda K, Toba K, Ouchi Y: "Effect of acute intake of red wine on flow-mediated vasodilatation of the brachial artery"Am J Cardiol. 88(12). 1457-60 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sudoh N, Toba K, Akishita M, Ako J, Hashimoto M, Iijima K, Kim S, Liang YQ, Ohike Y, Watanabe T, Yamazaki I, Yoshizumi M, Eto M, Ouchi Y: "Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats"Circulation. 103(5). 724-9 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogawa S, Fujita M, Ishii Y, Tsurukami H, Hirabayashi M, Ikeda K, Orimo A, Hosoi T, Ueda M, Nakamura T, Ouchi Y, Muramatsu M, Inoue S: "Impaired estrogen sensitivity in bone by inhibiting both estrogen receptor alpha and beta pathways"J Biol Chem.. 275(28). 21372-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Liang YQ, Kim S, Akishita M, Yoshizumi M, Hashimoto M, Ako J, Iijima K, Ohike Y, Watanabe T, Sudoh N, Toba K, Ouchi Y: "Estrogen attenuates ovariectomy-induced body weight gain through estrogen receptor beta-in the central nervous system"Circulation. 102(Suppl). II-349 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto M, Eto M, Akishita M, Kozaki K, Ako J, Iijima K, Kim S, Toba K, Yoshizumi M, Ouchi Y: "Corerlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men"Arterioscler Thromb Vasc Biol.. 19(11). 2795-800 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ouchi Y, Edt.: "Guideline of hormone replacement therapy in postmenopausal women"Medical Review Ltd., Tokyo, Japan. (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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