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Role of metallothionein on the progression of atherosclerosis and its application to medical care.

Research Project

Project/Area Number 21790136
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Environmental pharmacy
Research InstitutionAichi Gakuin University

Principal Investigator

FUJIWARA YASUYUKI  Aichi Gakuin University, 薬学部, 准教授 (40247482)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsメタロチオネイン / ノックアウトマウス / 血管内皮細胞 / カドミウム / ヒ素 / 動脈硬化症 / 血管毒性学 / 薬学 / 血管毒性 / 遺伝子欠損マウス
Research Abstract

Since metallothionein (MT) has a protective role against oxidative stress and inflammation, we considered that MT in the vascular tissue may be contribute to the protection against the development of atherosclerosis. In this study, we have utilized cell culture systems and animal models to determine whether MT in the vascular tissue can protect the onset and the progression of atherosclerosis. First, in this study period, we produced the MT-I, MT-II and apolipoprotein E (ApoE) deficient mice (MT-I/II/Apo-E triple-knockout mice) from ApoE knockout mice and MT-I and MT-II knockout mice. We also demonstrated the gene expression profile of human vascular endothelial cells exposed to arsenic and cadmium, which are risk factors for vascular lesions. In addition, we found that anti-platelet drug cilostazol strongly inhibits the vascular toxicity of arsenic and cadmium in vascular endothelial cells as a result of induction of metallothionein synthesis. These observations suggests that MT in the vascular tissue may contribute to the protection against the progression of atherosclerosis.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (13 results)

All 2011 2010 2009 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Protective effect of pretreatment with cilostazol on cytotoxicity of cadmium and arsenite in cultured vascular endothelial cells.2011

    • Author(s)
      Fujiwara Y., Banno H., Shinkai Y., Yamamoto C., Kaji T., Satoh M.
    • Journal Title

      J.Toxicol.Sci. 36

      Pages: 155-161

    • NAID

      10028101091

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray analysis of human coronary artery endothelial cells exposed to cadmium.2011

    • Author(s)
      Fujiwara Y., Honda A., Yamamoto C., Kaji T., Satoh M.
    • Journal Title

      J.Toxicol.Sci. 36

      Pages: 141-143

    • NAID

      10027420639

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray analysis of human coronary artery endothelial cells exposed to cadmium.2011

    • Author(s)
      Yasuyuki Fujiwara
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 36 Pages: 141-143

    • NAID

      10027420639

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of pretreatment with cilostazol on cytotoxicity of cadmium and arsenite in cultured vascular endothelial cells.2011

    • Author(s)
      Yasuyuki Fujiwara
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 36 Pages: 155-161

    • NAID

      10028101091

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray gene expression analysis of human vascular endothelial cells exposed to arsenite.2010

    • Author(s)
      Fujiwara, Y., Honda, A., Satoh, M.
    • Journal Title

      J.Toxicol.Sci. 35

      Pages: 275-278

    • NAID

      10026193591

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray gene expression analysis of human vascular endothelial cells exposed to arsenite2010

    • Author(s)
      Yasuyuki Fujiwara
    • Journal Title

      The Journal of Toxicological Sciences 35

      Pages: 275-278

    • NAID

      10026193591

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 疾病の予防と治療に向けたメタロチオネイン研究の新たな試み2010

    • Author(s)
      藤原泰之
    • Organizer
      第17回東海メタロチオネイン研究会
    • Place of Presentation
      岐阜薬科大学(岐阜)
    • Year and Date
      2010-12-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Induction of metallothionein synthesis by organometals and coordination compounds.2010

    • Author(s)
      藤原泰之
    • Organizer
      第20回金属の関与する生体関連反応シンポジウム
    • Place of Presentation
      徳島文理大学(徳島)
    • Year and Date
      2010-06-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 疾病の予防と治療に向けたメタロチオネイン研究の新たな試み2010

    • Author(s)
      藤原泰之、佐藤雅彦
    • Organizer
      第17回東海メタロチオネイン研究会
    • Place of Presentation
      岐阜
    • Related Report
      2010 Final Research Report
  • [Presentation] Induction of metallothionein synthesis by organometals and coordination compounds2010

    • Author(s)
      藤原泰之、佐藤雅彦
    • Organizer
      第20回金属の関与する生体関連反応シンポジウム
    • Place of Presentation
      徳島
    • Related Report
      2010 Final Research Report
  • [Presentation] 血管構成細胞におけるシロスタゾールによるメタロチオネイン誘導と血管保護作用2009

    • Author(s)
      藤原泰之、坂野博紀、鍜冶利幸、佐藤雅彦
    • Organizer
      メタロチオネインおよびメタルバイオサイエンス研究会2009
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] シロスタゾール前処理によるカドミウムおよび亜ヒ酸の細胞毒性の軽減2009

    • Author(s)
      藤原泰之、北川貴大、鍜冶利幸、佐藤雅彦
    • Organizer
      第36回日本トキシコロジー学会学術年会
    • Place of Presentation
      盛岡
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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