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2010 Fiscal Year Final Research Report

Novel molecular mechanisms for cardiotonic action, their involvement in diseases and application for treatment

Research Project

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Project/Area Number 19390211
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionMie University

Principal Investigator

ITO Masaaki  Mie University, 大学院・医学系研究科, 教授 (00223181)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Ryuji  三重大学, 大学院・医学系研究科, 助教 (60378346)
ONISHI Katsuya  三重大学, 大学院・医学系研究科, 助教 (40343222)
Project Period (FY) 2007 – 2010
Keywords心筋ミオシン / リン酸化 / ミオシン軽鎖キナーゼ / ミオシンホスファターゼ / 心不全
Research Abstract

The regulatory mechanism, function and the involvement in pathologic conditions of cardiac myosin light chain (MLC2) phosphorylation were investigated. Cardiac MLC2 was found to be phosphorylated by cardiac myosin light chain kinase (cMLCK), but not by smooth MLCK nor ZIP-kinase. However, cMLCK was not detected in several animal species, suggesting the existence of another (iso)forms of cardiac MLCK. Biochemical characteristics of cMLCK were different from those of smMLCK including the enzyme kinetics and the sensitivity for antagonists. The overexpression of cardiac myosin phosphatase in heart induced a reduction of MLC2 phosphorylation levels concomitant with a Ca^<2+> desensitization of contraction and decreased LV contractility, resulting in LV enlargement. Thus the phosphorylation of cardiac MLC2 plays a significant role in maintaining normal cardiac function. Agonist stimulation including endothelin-1 induced the expression of cMLCK and increased the phosphorylation level of MLC2. In addition, the expression of cMLCK and the phosphorylation levels of MLC2 were varied in several animal models, suggesting the phosphorylation of MLC2 might be involved in the several pathologic conditions in heart.

  • Research Products

    (32 results)

All 2011 2010 2009 2008 2007 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (17 results) Remarks (1 results)

  • [Journal Article] Efficacy of linear block at the left atrial roof in atrial fibrillation.2010

    • Author(s)
      Senga M, Fujii E, Sugiura S, Yamazato S, Sugiura E, Nakamura M, Miyahara M, Ito M.
    • Journal Title

      J.Cardiol. 55

      Pages: 322-327

    • Peer Reviewed
  • [Journal Article] Left ventricular contraction-relaxation coupling in normal, hypertrophic, and failing myocardium quantified by speckle-tracking global strain and strain rate imaging.2010

    • Author(s)
      Takamura T, Dohi K, Onishi K, Kurita T, Tanabe M, Tanigawa T, Isaka N, Ito M.
    • Journal Title

      J.Am.Soc.Echocardol. 23

      Pages: 747-754

    • Peer Reviewed
  • [Journal Article] Unique myocardial fibrosis pattern by late gadolinium enhanced magnetic resonance imaging in a patient with isolated noncompaction of the ventricular myocardium.2010

    • Author(s)
      Kurita T, Matsuoka K, Hoshida K, Nakamori S, Ichikawa Y, Tanigawa T, Onishi K, Nakamura T, Sakuma H, Ito M.
    • Journal Title

      Circ.J. 74

      Pages: 381-382

    • Peer Reviewed
  • [Journal Article] Overexpression of myosin phosphatase reduced Ca2+ sensitivity of contraction and impairs cardiac function.2010

    • Author(s)
      Mizutani H, Okamoto R, Moriki N, Konishi K, Taniguchi M, Fujita S, Dohi K, Onishi K, Suzuki M, Satoh S, Makino N, Itoh T, Hartshorne DJ, Ito M.
    • Journal Title

      Circ.J. 74

      Pages: 120-128

    • Peer Reviewed
  • [Journal Article] Regional myocardial perfusion reserve determined by quantitative analysis of myocardial perfusion MRI showed a good correlation with coronary flow velocity reserve by doppler flow wire.2009

    • Author(s)
      Kurita T, Sakuma H, Onishi K, Ishida M, Kitagawa K, Yamanaka T, Tanigawa T, Kitamura T, Takeda K, Ito M.
    • Journal Title

      Eur.Heart J. 30

      Pages: 444-452

    • Peer Reviewed
  • [Journal Article] Serum intact parathyroid hormone levels predict hospitalization for heart failure.2009

    • Author(s)
      Sugimoto T, Tanigawa T, Onishi K, Fujimoto N, Matsuda A, Nakamori S, Matsuoka K, Nakamura T, Koji T, Ito M.
    • Journal Title

      Heart 95

      Pages: 395-398

    • Peer Reviewed
  • [Journal Article] Hemodynamic characteristics of patients with diastolic heart failure and hypertension.2008

    • Author(s)
      Fujimoto N, Onishi K, Dohi K, Tanabe M, Kurita T, Takamura T, Yamada N, Nobori T, Ito M.
    • Journal Title

      Hypertens.Res. 31

      Pages: 1727-1735

    • Peer Reviewed
  • [Journal Article] Myosin phosphatase targeting subunit regulates mitosis by antagonizing polo-like kianase1.2008

    • Author(s)
      Yamashiro S, Yamakita Y, Totsukawa G, Goto H, Kaibuchi K, Ito M, Hartshorne DJ, Matsumura F.
    • Journal Title

      Dev.Cell 14

      Pages: 787-797

    • Peer Reviewed
  • [Journal Article] High glucose induces plasminogen activator inhibitor-1 expression through Rho/Rho-kinase- mediated NF-kB activation in bovine aortic endothelial cells.2008

    • Author(s)
      Iwasaki H, Okamoto R, Kato S, Konishi K, Mizutani H, Yamada N, Isaka N, Nakano T, Ito M.
    • Journal Title

      Atherosclerosis. 196

      Pages: 22-28

    • Peer Reviewed
  • [Journal Article] Correlation between late gadolinium enhancement and diastolic function in hypertrophic cardiomyopathy assessed by magnetic resonance imaging.2008

    • Author(s)
      Motoyasu M, Kurita T, Onishi K, Uemura S, Tanigawa T, Okinaka T, Takeda K, Nakano T, Ito M, Sakuma H.
    • Journal Title

      Circ.J. 72

      Pages: 378-383

    • Peer Reviewed
  • [Journal Article] Exaggerated hypertensive response to exercise in patients with diastolic heart failure.2008

    • Author(s)
      Kato S, Onishi K, Yamanaka T, Dohi K, Yamada N, Wada H, Ito M.
    • Journal Title

      Hypertens.Res. 31

      Pages: 679-684

    • Peer Reviewed
  • [Journal Article] Role of radial strain and displacement imaging to quantify wall motion dyssynchronyin patients with left ventricular mechanical dyssynchrony and chronic right ventricular pressure overlord.2008

    • Author(s)
      Dohi K, Onishi K, Gorcsan J III, Lopez-Candales A, Takamura T, Ota S, Yamada N, Ito M.
    • Journal Title

      Am.J.Cardiol. 101

      Pages: 1206-1212

    • Peer Reviewed
  • [Journal Article] Patients with a hypertensive response to exercise have impaired left vetricular diastolic function.2008

    • Author(s)
      Takamura T, Onishi K, Sugimoto T, Kurita T, Fujimoto N, Dohi K, Tanigawa T, Isaka N, Nobori T, Ito M.
    • Journal Title

      Hypertens.Res. 31

      Pages: 257-263

    • Peer Reviewed
  • [Journal Article] Impact of heart rate on mechanical dyssynchrony and left ventricular contractility in patients with heart failure and normal QRS duration.2007

    • Author(s)
      Kurita T, Onishi K, Dohi K, Tanabe M, Fujimoto N, Tanigawa T, Setsuda M, Isaka N, Nobori T, Ito M.
    • Journal Title

      Eur.J.Heart Fail. 9

      Pages: 637-643

    • Peer Reviewed
  • [Presentation] 心筋ミオシン軽鎖キナーゼの生化学的性状解析2011

    • Author(s)
      谷口正弥, 岡本隆二, 後藤至, 藤田聡,小西克尚, 中村真潮, 伊藤正明
    • Organizer
      第40回日本心脈管作動物質学会
    • Place of Presentation
      高松
    • Year and Date
      20110204-20110205
  • [Presentation] Long term prognostic value of stress perfusion CMR study for the prediction of cardiovascular death and nonfatal acute myocardial infarction in patients with or without preserved left ventricular ejection fraction.2010

    • Author(s)
      Kurita T, Sakuma H, Nakajima H, Kato S, Nakamori S, Kitagawa K, Onishi K, Ito M
    • Organizer
      American Heart Association 2010 Scientifc Sessions.
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      20101113-20101117
  • [Presentation] Impaired myocardial perfusion reserve in patients with fatty liver disease assessed by quantitative myocardial perfusion MRI.2010

    • Author(s)
      Nakamori S, Onishi K, Nakajima H, Kato S, Yoon YE, Kitagawa K, Dohi K, Nakamura M, Sakuma H, Ito M
    • Organizer
      American Heart Association 2010 Scientifc Sessions.
    • Place of Presentation
      Chicago, U.S.A.
    • Year and Date
      20101113-20101117
  • [Presentation] ラット高血圧自然発症モデルにおける各種降圧薬のミオシン軽鎖リン酸化レベルに対する効果2010

    • Author(s)
      小西克尚, 岡本隆二, 後藤至, 藤田聡, 谷口正弥, 水谷英夫, 宮原眞敏, 中村真潮, 伊藤正明
    • Organizer
      第33回日本高血圧学会総会
    • Place of Presentation
      福岡
    • Year and Date
      20101015-20101017
  • [Presentation] Role of hemodialytic therapy on left venatirular mechanical dyssynchrony in patients with end-stage renal failure quantified by speckle-tracking strain imaging.2010

    • Author(s)
      Dohi K, Murata T, Onishi K, Sugiura E, Sugimoto T, Yamada N, Nomura S, Miyahara M, Nakamura M, Ito M
    • Organizer
      European Society of Cardiology Congress 2010.
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      20100828-20100901
  • [Presentation] Diagnostic utility of serum intact parathyroid hormone in predicting impaired cardiac hemodynamics combined with brain natriuretic peptide in patients with heart failure.2010

    • Author(s)
      Sugimoto T, Dohi K, Nakajima H, Ichikawa K, Nakamori S, Tanabe M, Onishi K, Miyahara M, Nakamura M, Ito M
    • Organizer
      European Society of Cardiology Congress 2010.
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      20100828-20100901
  • [Presentation] Olmesartan, hydralazine and carvedilol decrease myosin light chain phosphorylation in vascular smooth muscle and Partly Exert Their Antihypertensive Effects.2010

    • Author(s)
      Konishi K, Okamoto R, Fujita S, Taniguchi M, Mizutani H, Miyahara M, Nakamura M, Ito M
    • Organizer
      第42回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      20100715-20100716
  • [Presentation] ラット高血圧自然発症モデルに対する種々の降圧薬の効果とミオシン軽鎖リン酸レベルの変化とその機序に関する検討2010

    • Author(s)
      小西克尚, 岡本隆二, 藤田聡, 谷口正弥, 伊藤正明
    • Organizer
      第39回日本心脈管作動物質学会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-02-05
  • [Presentation] Long term prognostic value of stress perfusion CMR study for the prediction of cardiovascular death and nonfatal acute myocardial infarction in 1009 asian patients.2009

    • Author(s)
      Kurita T, Sakuma H, Nakajima H, Kato S, Miyagi H, Nakamori S, Kitagawa K, Onishi K, Nakamura M, Ito M
    • Organizer
      American Heart Association 2009 Scientifc Sessions.
    • Place of Presentation
      Orlando, U.S.A.
    • Year and Date
      20091114-20091118
  • [Presentation] Human atrial natriuretic peptide preserved infract-related myocardial blood flow quantified by perfusion MRI in patients with acute myocardial infarction.2009

    • Author(s)
      Kurita T, Tanigawa T, Sakuma H, Sato K, Nakajima H, Nakamori S, Ichikawa Y, Kitagawa K, Matsuoka K, Onishi K, Nakamura T, Ito M
    • Organizer
      American Heart Association 2009 Scientifc Sessions.
    • Place of Presentation
      Orlando, U.S.A.
    • Year and Date
      20091114-20091118
  • [Presentation] Coupling of systolic and diastolic function and regional synchrony in normal, hypertrophic, and failing myocardium quantified by speckle-tracking echocardiography.2009

    • Author(s)
      Dohi K, Onishi K, Takamura T, Sugiura E, Nakajima H, Ichikawa K, Tanabe M, Miyahara M, Nakamura M, Ito M
    • Organizer
      European Society of Cardiology Congress 2009.
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      20090829-20090902
  • [Presentation] Presence of myocardial scar is strongly associated with abnormal regional myocardial blood flow in hypertrophic cardiomyopathy.2009

    • Author(s)
      Nakajima H, Onishi K, Kurita T, Ishida M, Nagata M, Kitagawa K, Dohi K, Nakamura M, Sakuma H, Ito M
    • Organizer
      European Society of Cardiology Congress 2009.
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      20090829-20090902
  • [Presentation] Quantification of left ventricular contraction and relaxation in patients with diastolic heart failure by speckle-tracking strain and strain rateechocardiography.2009

    • Author(s)
      Ogawa E, Dohi K, Onishi K, Takamura T, Nakajima H, IchikawaK, Tanabe M, Tamada H, Miyahara M, Nakamura M, Ito M
    • Organizer
      第73回日本循環器学会総会・学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20090320-20090323
  • [Presentation] Quantification of left ventricular mechanical dyssynchrony in normal, hypertrophied, and dilated myocardium quantified by speckle-tracking strain echocardiography.2009

    • Author(s)
      Dohi K, Onishi K, Takamura T, Ogawa E, Nakajima H, Ichikawa K, Tanabe M, Tamada H, Miyahara M, Nakamura M, Ito M
    • Organizer
      第73回日本循環器学会総会・学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20090320-20090323
  • [Presentation] Subendmyocardial perfusion reserve correlated with left ventricular diastolic function in patients with various types of left ventricular hypertrophy.2008

    • Author(s)
      Kurita T, Onishi K, Sakuma H, Takamura T, Nagata M, Nakajima H, Ishida M, Fujimoto N, Dohi K, Takeda K, Ito M
    • Organizer
      American Heart Association 2008 Scientifc Sessions.
    • Place of Presentation
      New Orleans, U.S.A.
    • Year and Date
      20081108-20081112
  • [Presentation] Hypertension plays an important role on the impairment of myocardial perfusion reserve determined by quantitative analysis of myocardial perfusion MRI.2008

    • Author(s)
      Nakajima H, Onishi K, Kurita T, Ishida M, Takamura T, Ishida N, Dohi K, Nakamura M, Sakuma H, Ito M
    • Organizer
      American Heart Association 2008 Scientifc Sessions.
    • Place of Presentation
      New Orleans, U.S.A.
    • Year and Date
      20081108-20081112
  • [Presentation] 心筋ミオシンホスファターゼの分子性状とその機能2008

    • Author(s)
      水谷英夫, 森木宣行, 岡本隆二, 井阪直樹,中野赳, 伊藤正明, 大西勝也, 鈴木昇, 佐藤真司, 牧野直樹, David Hartshorne.
    • Organizer
      第37回日本心脈管作動物質学会
    • Place of Presentation
      仙台
    • Year and Date
      2008-02-02
  • [Remarks] ホームページ等

    • URL

      http://www.medic.mie-u.ac.jp/naika1/classroom/research/a01.html

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Published: 2012-01-26   Modified: 2016-04-21  

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