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Role of ROCK activity in cardiovascular diseases: a translational research

Research Project

Project/Area Number 23591043
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionHiroshima University

Principal Investigator

NOMA KENSUKE  広島大学, 原爆放射線医科学研究所, 助教 (00379893)

Co-Investigator(Kenkyū-buntansha) HIGASHI Yukihito  広島大学, 原爆放射線医科学研究所, 教授 (40346490)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsROCK / 血管内皮機能 / 心血管障害 / 脳梗塞 / 血管機能 / eNOS / 国際情報交流 米国 / トランスレーショナルリサーチ / シグナル伝達 / 循環器・高血圧 / 発現制御 / 臨床
Research Abstract

From endothelial cellular and murine experiments, we have revealed that ROCK2, one of ROCK isoforms, could destabilize eNOS mRNA via ROCK2-mediated phosphorylation of eEF1A and binding of ROCK2 with 3'-UTR of eNOS mRNA. In addition, we have further found that ROCK2 could regulate cardiac hypertrophy via modulation of FHL2.
From clinical studies, we have revealed that leukocyte ROCK activity could reflect vascular function and could be quite a useful biomarker to predict cardiovascular events.
Therefore, we concluded from such a translational study that ROCK2 could be a promising target in patients with cardiovascular diseases and leukocyte ROCK activity could be a useful biomarker to evaluate vascular function.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (44 results)

All 2014 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results,  Open Access: 1 results) Presentation (21 results) (of which Invited: 3 results) Book (2 results)

  • [Journal Article] Rho-associated kinase is a predictor of a predictor of cardiovascular outcomes2013

    • Author(s)
      Kajikawa M, Noma K, Maruhashi T, Mikami S, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Liao JK, Higashi Y.
    • Journal Title

      Hypertension

      Volume: 64 Pages: 856-864

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2.2013

    • Author(s)
      Noma K, Okamoto R, Li Y, Hiroi Y, Liu PY, Taniguchi M, Ito M, Liao JK.
    • Journal Title

      FASEB J.

      Volume: 27 Issue: 4 Pages: 1439-1449

    • DOI

      10.1096/fj.12-217018

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rho-associated kinase is a predictor of a predictor of cardiovascular outcomes.2013

    • Author(s)
      Kajikawa M, Noma K, Maruhashi T, Mikami S, Iwamoto Y, Iwamoto A, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Nakashima A, Goto C, Liao JK, Higashi Y.
    • Journal Title

      Hypertension.

      Volume: 64 Issue: 4 Pages: 856-864

    • DOI

      10.1161/hypertensionaha.113.02296

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flow-Mediated Vasodilation and Anatomical Variation of the Brachial Artery (Double Brachial Artery) in Healthy Subjects and Patients with Cardiovascular Diseases.2013

    • Author(s)
      Fujii Y, Teragawa H, Soga J, Idei N, Fujimura N, Maruhashi T, Mikami S, Iwamoto Y, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Higashi Y.
    • Journal Title

      Circ J

      Volume: 77 Pages: 1073-1080

    • NAID

      10031139013

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2.2013

    • Author(s)
      Noma K, Okamoto R, Li Y, Hiroi Y, Liu PY, Taniguchi M, Ito M, Liao JK.
    • Journal Title

      FASEB J

      Volume: 27 Pages: 1439-1449

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Novel Noninvasive and Simple Method for Assessment of Endothelial Function:Enclosed Zone Flow-Mediated Vasodilation (ezFMD) Using an Oscillation Amplitude Measurement.2013

    • Author(s)
      Idei N, Ukawa T, Kajikawa M, Iwamoto Y, Fujimura N, Maruhashi T, Mikami S, Matsumoto T, Kihara Y, Chayama K, Noma K, Nakashima A, Takayanagi T, Morimoto H, Tsuji T, Higashi Y.
    • Journal Title

      Circ J

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nitroglycerine-induced Vasodilation for Assessment of Vascular Function: A Comparison with Flow-mediated Vasodilation.2013

    • Author(s)
      Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Higashi Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mineralocorticoid Receptor Blocker Eplerenone Improves Endothelial Function and Inhibits Rho-associated Kinase Activity in Patients With Hypertension2012

    • Author(s)
      Fujimura N, Noma K, Hata T, Soga J, Hidaka T, Idei N, Fujii Y, Mikami S, Maruhashi T, Iwamoto Y, Kihara Y, Chayama K, Kato H, Liao JK, Higashi Y.
    • Journal Title

      Clin Pharmacol Ther

      Volume: 91 Issue: 2 Pages: 289-297

    • DOI

      10.1038/clpt.2011.227

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Striking Crosstalk of ROCK Signaling with Endothelial Function2012

    • Author(s)
      Noma K, Kihara Y, Higashi Y.
    • Journal Title

      J Cardiol

      Volume: 60 Pages: 1-6

    • NAID

      10031187760

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] How to Use Ezetimibe as an Anti-Atherogenic Agent via Inhibition of Rho-Kinase2012

    • Author(s)
      Noma K, Higashi Y.
    • Journal Title

      Circ J

      Volume: 76 Pages: 1836-1837

    • NAID

      10030504234

    • URL

      https://www.jstage.jst.go.jp/browse/circj/

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intima-Media Thickness of Brachial Artery, Vascular Function, and Cardiovascular Risk Factors.2012

    • Author(s)
      Iwamoto Y, Maruhash T, Fujii Y, Idei N, Fujimura N, Mikami S, Kajikawa M, Matsumoto T, Kihara Y, Chayama K, Noma K, Nakashima A, Higashi Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32 Issue: 9 Pages: 2295-2303

    • DOI

      10.1161/atvbaha.112.249680

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hyperbilirubinemia, Augmentation of Endothelial Function and Decrease in Oxidative Stress in Gilbert Syndrome.2012

    • Author(s)
      Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Kihara Y, Chayama K, Noma K, Nakashima A, Tomiyama H, Takase B, Yamashina A, Higashi Y.
    • Journal Title

      Circulation

      Volume: 126 Issue: 5 Pages: 598-603

    • DOI

      10.1161/circulationaha.112.105775

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Geranylgeranylacetone, Hsp90/AMPK/eNOS/NO Pathway, and Endothelial Function in Humans.2012

    • Author(s)
      Fujimura N, Jitsuiki D, Maruhashi T, Mikami S, Iwamoto Y, Kajikawa M, Chayama K, Kihara Y, Noma K, Goto C, Higashi Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32 Pages: 153-160

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] ROCK Study Group. Rho-associated kinase activity, endothelial function, and cardiovascular risk factors2011

    • Author(s)
      Higashi Y(14人中14番目)
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Issue: 10 Pages: 2353-9

    • DOI

      10.1161/atvbaha.111.227892

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular Function and Circulating Progenitor Cells in Thromboangitis Obliterans (Buerger’s Disease) and Atherosclerosis Obliterans.2011

    • Author(s)
      Idei N, Nishioka K, Soga J, Hidaka T, Hata T, Fujii Y, Fujimura N, Maruhashi T, Mikami S, Teragawa H, Kihara Y, Noma K, Chayama K, Higashi Y.
    • Journal Title

      Hypertension

      Volume: 57 Pages: 70-78

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autologous Bone-Marrow Mononuclear Cell Implantation Reduces Long-Term Major Amputation Risk in Patients with Critical Limb Ischemia: A Comparison of Atherosclerotic Peripheral Arterial Disease and Buerger's Disease.2011

    • Author(s)
      Idei N, Soga J, Hata T, Fujii Y, Mikami S, Maruhashi T, Nishioka K, Hidaka T, Kihara Y, Chowdfury M, Noma K, Taguchi A, Chayama K, Sueda T, Higashi Y.
    • Journal Title

      Circ Cardiovasc Interv

      Volume: 4 Pages: 15-25

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Notch1 in Bone Marrow-derived Cells Mediates Cardiac Repair Following Myocardial Infarction.2011

    • Author(s)
      Li Y, Hiroi Y, Ngoy S, Okamoto R, Noma K, Wang CY, Wang HW, Zhou Q, Radtke F, Liao R, Liao JK.
    • Journal Title

      Circulation

      Volume: 123 Pages: 866-876

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of Rho kinase isoforms in Murine Allergic Airway Responses.2011

    • Author(s)
      Zhu M, Liu PY, Kasahara DI, Williams AS, Verbout NG, Halayko AJ, Fedulov A, Shoji T, Williams ES, Noma K, Shore SA, Liao JK.
    • Journal Title

      Eur Respir J

      Volume: 38 Pages: 841-850

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rho-Associated Kinase (ROCK) Activity, Endothelial Function and Cardiovascular Risk Factors.2011

    • Author(s)
      Soga J, Noma K, Hata T, Hidaka T, Fujii Y, Idei N, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Chayama K, MD, Kato H, Liao JK, Higashi Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Pages: 2353-2359

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Color Doppler Flows of Corkscrew Collaterals in Thromboangiitis Obliterans (Buerger's Disease) Using Color Duplex Ultrasonography.2011

    • Author(s)
      Fujii Y, Soga J, Hidaka T, Hata T, Idei N, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Noma K, Higashi Y.
    • Journal Title

      J Am Coll Cardiol

      Volume: 57 Pages: 2539-2539

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Flow-mediated vasodilation is augmented in a corkscrew collateral artery compared with that in a native artery in patients with thromboangiitis obliterans (Buerger disease).2011

    • Author(s)
      Fujii Y, Fujimura N, Mikami S, Maruhashi T, Kihara Y, Chayama K, Noma K, Higashi Y.
    • Journal Title

      J Vasc Surg

      Volume: 54 Pages: 1689-1697

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Destabilization of eNOS mRNA via ROCK2-mediated eEF1A1 phospohrylation2014

    • Author(s)
      野間玄督,木原康樹,東幸仁
    • Organizer
      第3回臨床高血圧フォーラム
    • Place of Presentation
      広島,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of ROCK in sustained vasoconstriction in patients with essential hypertension2014

    • Author(s)
      Noma K, Goto C, Kihara Y, Liao JK, Higashi Y.
    • Organizer
      The 18^<th> International Vascular Biology Meeting (IVBM2014)
    • Place of Presentation
      京都,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] ROCK as a modulator of sustained vasoconstriction of resistance artery in patients with essential hypertension2014

    • Author(s)
      Noma K, Goto C, Kihara Y, Liao JK, Higashi Y.
    • Organizer
      第78回日本循環器学会総会・学術集会
    • Place of Presentation
      東京,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] ROCK as a Modulator of Sustained Vasoconstriction of ResistanceArtery in Patients with Essential Hypertension.2014

    • Author(s)
      Noma K, Goto C, Kihara Y, Liao JK, Higashi Y.
    • Organizer
      第78回日本循環器学会総会・学術集会.
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of ROCK in Sustained Arterial Vasoconstriction in Patients with Essential Hypertension.2014

    • Author(s)
      Noma K, Goto C, Kihara Y, Liao JK, Higashi Y.
    • Organizer
      The 18th International Vascular Biology Meeting (IVBM 2014)
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Destabilization of eNOS mRNA via ROCK2-mediated eEF1A1 phosphorylation.2014

    • Author(s)
      野間玄督, 木原康樹, 東 幸仁.
    • Organizer
      第3回臨床高血圧フォーラム
    • Place of Presentation
      広島
    • Related Report
      2013 Annual Research Report
  • [Presentation] ROCK Activity and Endothelial Function: Potential Candidates for Vascular and Anti-aging Biomarkers2014

    • Author(s)
      野間玄督, 木原康樹, 東 幸仁.
    • Organizer
      第14回日本抗加齢医学会総会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Clinical Impact of ROCK in Sustained Vasoconstriction in Patients with Essential Hypertension.2014

    • Author(s)
      Noma K, Goto C, Kihara Y, Higashi Y.
    • Organizer
      第35回日本循環制御医学会総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of ROCK in sustained vasoconstriction of resistance artery in patients with essential hypertension2013

    • Author(s)
      Noma K, Goto C, Kihara Y, Liao JK, Higashi Y.
    • Organizer
      Scientific Sessions 2013, American Heart Association
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of eNOS mRNA stability via ROCK2-mediated eEF1A1 phosphorylation2013

    • Author(s)
      野間玄督、木原康樹、東幸仁
    • Organizer
      第21回日本血管生物医学会学術集会
    • Place of Presentation
      大阪,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of eNOS mRNA stability via ROCK2-mediated eEF1A1 phosphorylation.2013

    • Author(s)
      野間玄督、木原康樹、東幸仁
    • Organizer
      第21回日本血管生物医学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of ROCK in Sustained Vasoconstriction of Resistance Artery in Patients with Essential Hypertension.2013

    • Author(s)
      Noma K, Goto C, Kihara Y, Liao JK, Higashi Y.
    • Organizer
      Scientific Sessions 2013, American Heart Association.
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Clinical Evaluation of Endothelial Function and Dysfunction2013

    • Author(s)
      野間玄督, 木原康樹, 東 幸仁.
    • Organizer
      第35回EMBC学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ROCK関連研究の新たな展開2012

    • Author(s)
      野間玄督,東幸仁
    • Organizer
      第41回日本心脈管作動物質学会
    • Place of Presentation
      秋田,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] ROCK関連研究の新たな展開2012

    • Author(s)
      野間玄督, 東幸仁
    • Organizer
      第41回日本心脈管作動物質学会(招待講演)
    • Place of Presentation
      秋田
    • Related Report
      2011 Research-status Report
  • [Presentation] Role of ROCK in sustained vasoconstriction in patients with essential hypertension.2012

    • Author(s)
      野間玄督, 東幸仁
    • Organizer
      第8回宮崎サイエンスキャンプ
    • Place of Presentation
      宮崎
    • Related Report
      2011 Research-status Report
  • [Presentation] 心血管疾患におけるROCK活性:メディエーターそしてマーカーとしての役割2011

    • Author(s)
      野間玄督,東幸仁,木原康樹
    • Organizer
      第19回日本血管生物医学会学術集会
    • Place of Presentation
      東京,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] Leukocyte ROCK activity : a potential candidate for vascular and anti-aging biomarker2011

    • Author(s)
      野間玄督,木原康樹,東幸仁
    • Organizer
      アンチエイジングフェスタ2011
    • Place of Presentation
      大阪,日本
    • Related Report
      2013 Final Research Report
  • [Presentation] 心血管疾患におけるROCK活性:メディエーターそしてマーカーとしての役割2011

    • Author(s)
      野間玄督, 東幸仁, 木原康樹
    • Organizer
      第19回日本血管生物医学会学術集会(招待講演)
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Leukocyte ROCK Activity: a Potential Candidate for Vascular and Anti-aging Biomarker.2011

    • Author(s)
      野間玄督, 木原康樹, 東幸仁
    • Organizer
      アンチエイジングフェスタ2011
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] Regulation of eNOS mRNA stability vie ROCK2-mediated phosphorylation of eEF1A

    • Author(s)
      野間玄督,廣井透雄,James K. Liao、,東 幸仁
    • Organizer
      第9回宮崎サイエンスキャンプ
    • Place of Presentation
      宮崎
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] ICU看護実践ハンドブック2013

    • Author(s)
      野間玄督,東 幸仁
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2012 Research-status Report
  • [Book] 糖尿病と酸化ストレス2011

    • Author(s)
      野間玄督, 東幸仁
    • Total Pages
      5
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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