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  1. 医歯学総合研究科
  2. 医歯学総合研究科・博士論文

Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis

http://hdl.handle.net/10232/00030839
http://hdl.handle.net/10232/00030839
c6b535d8-2fd3-406d-8f52-cfc7be1c6126
名前 / ファイル ライセンス アクション
Diss_佐々木_雄一_ISK523_2019.pdf Diss_佐々木_雄一_ISK523_2019 (6.2 MB)
license.icon
Abstract_佐々木_雄一_4518810081_2019.pdf Abstract_佐々木_雄一_4518810081_2019 (69.4 kB)
Result_Sasaki_Yuichi_isk_523.pdf Result_Sasaki_Yuichi_isk_523 (1.0 MB)
Comments_Sasaki_Yuichi_isk_523.pdf Comments_Sasaki_Yuichi_isk_523 (451.8 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2019-11-26
タイトル
タイトル Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis
別言語のタイトル
その他のタイトル エストロゲン-SIRT1系は閉経に伴う血管老化・動脈硬化に対する動脈保護において重要な役割を果たす
著者 佐々木, 雄一

× 佐々木, 雄一

WEKO 134580

佐々木, 雄一

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著者よみ
姓名 ササキ, ユウイチ
別言語の著者
姓名 SASAKI, Yuichi
言語
言語 eng
キーワード
主題言語 en
主題Scheme Other
主題 Estrogen
キーワード
主題言語 en
主題Scheme Other
主題 eNOS
キーワード
主題言語 en
主題Scheme Other
主題 SIRT1
キーワード
主題言語 en
主題Scheme Other
主題 Atherosclerosis
キーワード
主題言語 en
主題Scheme Other
主題 Arterial senescence
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
要約(Abstract)
内容記述タイプ Other
内容記述 Aim: Menopause causes arterial senescence and atherosclerotic development through decrease of estrogen. Recently, histone deacetylase SIRT1 has been reported to have protective effects against arterial senescence and atherosclerosis. However, the relationship between estrogen and SIRT1 in the context of menopause-induced arterial senescence is not well understood. The present study aims to investigate whether SIRT1 is involved in the etiology of menopause-induced arterial senescence and atherosclerotic development.
Methods: Twelve-week old female apolipoprotein E-knockout (ApoE-KO) mice underwent ovariectomy (OVX) or sham surgery.
Results: SIRT1 expression and endothelial nitric oxide synthase (eNOS) activation in the aorta were significantly lower in OVX mice than they were in sham mice (OVX vs. sham, n= 5 per group). Senescence-associated β-galactosidase activity, protein expression of Ac-p53 and PAI-1, and aortic atherosclerosis lesions were significantly greater in OVX mice than they were in sham mice. Administration of 17β-estradiol (E2) for eight weeks to OVX mice restored aortic SIRT1 expression, activated eNOS, and retarded OVX-induced arterial senescence and atherosclerotic development (E2 vs. control, n= 5 per group). The effects of E2 on SIRT1 upregulation, antisenescence and anti-atherosclerosis were attenuated by administration of a SIRT1 inhibitor, sirtinol. In vitro experiment using human endothelial cells demonstrated that E2 also increased SIRT1 expression and retarded oxidized low density lipoprotein-induced premature senescence, which were also abolished by sirtinol. These results suggested that estrogen modulated arterial senescence and atherosclerosis through SIRT1. Additionally a selective estrogen receptor modulator (SERM), bazedoxifene, also augmented SIRT1 and inhibited arterial senescence and atherosclerotic development (SERM vs. control, n= 3 per group).
Conclusions: Downregulation of SIRT1 causes OVX-induced arterial senescence and atherosclerosis in ApoEKO mice. Administration of estrogen or SERM enables OVX mice to restore these alterations by SIRT1 induction.
要約(Abstract)
内容記述タイプ Other
内容記述 Yuichi Sasaki, Yoshiyuki Ikeda, Takahiro Miyauchi, Yoshihiro Uchikado, Yuichi Akasaki and Mitsuru Ohishi
Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis
Journal of Atherosclerosis and Thrombosis, 27(1)pp.47-59, 2020
doi.org/10.5551/jat.47993
収録雑誌名 Journal of Atherosclerosis and Thrombosis

巻 27, 号 1, p. 47-59, 発行日 2020
作成日
日付 2019-10-03
DOI
識別子タイプ DOI
DOI 10.5551/jat.47993
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
NDC
主題Scheme NDC
主題 490
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文全文
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文要旨
ファイル(説明)
内容記述タイプ Other
内容記述 最終試験結果の要旨
ファイル(説明)
内容記述タイプ Other
内容記述 論文審査の要旨
公開者・出版者
出版者 Japan Atherosclerosis Society
公開者・出版者
出版者 鹿児島大学
公開者よみ
公開者よみ カゴシマ ダイガク
公開者別名
公開者別名 Kagoshima University
備考
備考 【指導教員:大石充】
date.appl
【学位申請日】2019-06-05
学位名
学位名 博士(医学)Doctor of Philosophy in Medical Science
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 17701
学位授与機関名 鹿児島大学
学位授与年月日
学位授与年月日 2019-10-17
学位授与番号
学位授与番号 甲総研第523号
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