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2012 Fiscal Year Final Research Report

The role of SmgGDS in the pleiotropic effects by statins

Research Project

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Project/Area Number 23659071
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

SHIMOKAWA Hiroaki  東北大学, 大学院・医学系研究科, 教授 (00235681)

Co-Investigator(Kenkyū-buntansha) SATOH Kimio  東北大学, 高等教育開発推進センター, 准教授 (80436120)
Project Period (FY) 2011 – 2012
Keywordsシグナル伝達 / スタチン / 低分子量G蛋白
Research Abstract

We tested our hypothesis that small GTP-binding protein GDP dissociation stimulator (SmgGDS) plays a crucial role in the molecular mechanisms of the Rac1 signaling pathway inhibition by3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in endothelial cells. In the present study, we demonstrated that statins exert their pleiotropic effects through SmgGDS upregulation with a resultant Rac1 degradation and reduced oxidative stress in animals and humans.

  • Research Products

    (26 results)

All 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (9 results) Book (6 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Statins exert pleiotropic effects through SmgGDS up-regulation with a resultant Rac1 degradation2013

    • Author(s)
      Tanaka S, Fukumoto Y, Nochioka K, Minami T, Kudo S, Shiba N, Takai Y, Williams CL, Liao JK, Shimokawa H.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: (in press)

    • DOI

      doi:10.1161/ATVBAHA.112.300922

    • Peer Reviewed
  • [Journal Article] Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications and prognostic impact -Multicenter registry study of the Japanese Coronary Spasm Association-2013

    • Author(s)
      Takagi Y, Yasuda S, Takahashi J, Tsunoda R, Ogata Y, Seki A, Sumiyoshi T, Matsui M, Goto T, Tanabe Y, Sueda S, Sato T, Ogawa S, Kubo N, Momomura S, Ogawa H, Shimokawa H.
    • Journal Title

      Eur Heart J

      Volume: 34 Pages: 258-267

    • DOI

      doi:10.1093/eurheartj/ehs199.

    • Peer Reviewed
  • [Journal Article] Plasma cyclophilin A is a novel biomarker for coronary artery disease2013

    • Author(s)
      Satoh K, Fukumoto Y, Sugimura K, Miura Y, Aoki T, Nochioka K, Tatebe S, Miyamichi-Yamamoto S, Shimizu T, Osaki S, Takagi Y, Tsuburaya R, Ito Y, Matsumoto Y, Nakayama M, Takeda M, Takahashi J, Ito K, Yasuda S, Shimokawa H.
    • Journal Title

      Circ J

      Volume: 77 Pages: 447-455

    • DOI

      doi:10.1253/circj.CJ-12-0805

    • Peer Reviewed
  • [Journal Article] Essential role of the bone marrow for microvascular endothelial and metabolic functions in mice2012

    • Author(s)
      Nakajima S, Ohashi J, Sawada A, Noda K, Fukumoto Y, Shimokawa H.
    • Journal Title

      Circ Res

      Volume: 111 Pages: 87-96

    • DOI

      doi:10.1161/CIRCRESAHA.112.270215.

    • Peer Reviewed
  • [Journal Article] The mechanisms for enhanced endothelium-derived hyperpolarizing factor-mediated responses in microvessels in mice2012

    • Author(s)
      Ohashi J, Sawada A, Nakajima S, Noda K, Takaki A, Shimokawa H.
    • Journal Title

      Circ J

      Volume: 76 Pages: 1768-1779

    • DOI

      doi:10.1253/circj.CJ-12-0197

    • Peer Reviewed
  • [Journal Article] Long-term treatment with nifedipine suppresses coronary hyperconstrcting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo: Possible involvement of Rho-kinase pathway-2012

    • Author(s)
      Tsuburaya R, Yasuda S, Shiroto T, Ito Y, Gao JY, Aizawa K, Kikuchi Y, Ito K, Takahashi J, Ishibashi-Ueda H, Shimokawa H.
    • Journal Title

      Eur Heart J

      Volume: 33 Pages: 791-799

    • DOI

      doi:10.1093/eurheartj/ehr145.

    • Peer Reviewed
  • [Journal Article] Vascular-derived reactive oxygen species for homeostasis and diseases2011

    • Author(s)
      Satoh K, Shimokawa H.
    • Journal Title

      Nitric Oxide

      Volume: 25 Pages: 211-215

    • DOI

      doi:10.1016/j.niox.2011.04.005.

    • Peer Reviewed
  • [Journal Article] Rho-kinase: Important new therapeutic target in cardiovascular diseases2011

    • Author(s)
      Satoh K, Fukumoto Y, Shimokawa H.
    • Journal Title

      Am J Physiol

      Volume: 301 Pages: H287-296

    • DOI

      doi:10.1152/ajpheart.00327.2011.

    • Peer Reviewed
  • [Presentation] Recent progress in endothelial research2013

    • Author(s)
      Shimokawa H
    • Organizer
      Invited lecture at Royal Adelaide Hospital
    • Place of Presentation
      Adelaide, Australia
    • Year and Date
      2013-04-30
  • [Presentation] Update on coronary spasm2013

    • Author(s)
      Shimokawa H
    • Organizer
      Rome Cardiology Forum 2012
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2013-03-30
  • [Presentation] Rho-kinase as an important new therapeutic target in cardiovascular medicine2013

    • Author(s)
      Shimokawa H.
    • Organizer
      Invited lecture at the San Raffaele University
    • Place of Presentation
      Milano, Italy
    • Year and Date
      2013-03-30
  • [Presentation] The Great East Japan Earthquake Disaster and cardiovascular diseases2012

    • Author(s)
      Shimokawa H
    • Organizer
      European Society of Cardiology Congress
    • Place of Presentation
      Munich, Germany
    • Year and Date
      20120825-29
  • [Presentation] Role of Rho/Rho-kinase pathway in the cardiovascular system2012

    • Author(s)
      Shimokawa H.
    • Organizer
      6th European Congress of Pharmacology
    • Place of Presentation
      Granada, Spain
    • Year and Date
      2012-07-19
  • [Presentation] Present status & future perspectives of heart failure in Japan2012

    • Author(s)
      Shimokawa H.
    • Organizer
      Invited lecture at the Flinders Medical Center
    • Place of Presentation
      Adelaide, Australia
    • Year and Date
      2012-05-02
  • [Presentation] Coronary spasm in 2012: Mechanisms and treatment2012

    • Author(s)
      Shimokawa H
    • Organizer
      Invited lecture at the Cardiac Society of Australia & New Zealand Meeting
    • Place of Presentation
      Adelaide, Australia
    • Year and Date
      2012-05-01
  • [Presentation] Rho-kinase as an important CV therapeutic target2012

    • Author(s)
      Shimokawa H
    • Organizer
      Invited lecture at Medical Grand Round of the Queen Elizabeth Hospital
    • Place of Presentation
      Adelaide, Australia
    • Year and Date
      2012-05-01
  • [Presentation] Recent progress in endothelial research2012

    • Author(s)
      Shimokawa H
    • Organizer
      Invited lecture at the Cardiology Academic Meeting of the Queen Elizabeth Hospital
    • Place of Presentation
      Adelaide, Australia
    • Year and Date
      2012-05-01
  • [Book] 日本人の虚血性心疾患に関する基礎的・臨床的研究2013

    • Author(s)
      下川宏明
    • Total Pages
      2237-2242
    • Publisher
      日本医師会雑誌141
  • [Book] 内皮由来過分極因子の医学的意義.血栓と循環2012

    • Author(s)
      下川宏明、神戸茂雄
    • Total Pages
      20:165-169
    • Publisher
      メディカルレビュー社
  • [Book] 大震災と循環器・呼吸器疾患(序文).呼吸と循環2012

    • Author(s)
      下川宏明
    • Total Pages
      60:895-895
    • Publisher
      医学書院
  • [Book] H_2O_2が制御する血管弛緩反応2012

    • Author(s)
      下川宏明
    • Total Pages
      139:229-235
    • Publisher
      日本薬理学雑誌
  • [Book] 肺高血圧診療の進歩をみる.特集にあたって2012

    • Author(s)
      下川宏明
    • Total Pages
      8:1-2
    • Publisher
      Vascular Medicine
  • [Book] 医学論文の書き方.Circulation Journal編集長からのアドバイス-心臓2011

    • Author(s)
      下川宏明
    • Total Pages
      43:1414-1416
    • Publisher
      日本心臓財団
  • [Remarks]

    • URL

      http://www.cardio.med.tohoku.ac.jp/index.html

  • [Patent(Industrial Property Rights)] サイクロフィリンAによる心血管疾患の検査方法2012

    • Inventor(s)
      下川宏明、佐藤公雄
    • Industrial Property Rights Holder
      下川宏明、佐藤公雄(国立大学法人東北大学)
    • Industrial Property Number
      特許、特願2012-239615
    • Filing Date
      2012-10-30
  • [Patent(Industrial Property Rights)] スタチンの用法、用量を決定する方法2011

    • Inventor(s)
      下川宏明、田中眞一
    • Industrial Property Rights Holder
      下川宏明、田中眞一
    • Industrial Property Number
      特許、特願2011-197906
    • Filing Date
      2011-09-12

URL: 

Published: 2014-09-25  

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