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Development of new therapy for heart failure and arrhythmia by correction of signal transduction within cardiac ryanodine receptor

Research Project

Project/Area Number 20390226
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YANO Masafumi  Yamaguchi University, 医学部・附属病院, 講師 (90294628)

Co-Investigator(Kenkyū-buntansha) IKEDA Yasuhiro  山口大学, 大学院・医学系研究科, 助教 (00260349)
KOBAYASHI Shigeki  山口大学, 医学部・附属病院, 助教 (90397993)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2009: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2008: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywords筋小胞体 / カルシウム / 心不全 / 致死的不整脈 / リアノジン受容体 / 点突然変異
Research Abstract

The defective inter-domain interaction between N-terminal and central domains within RyR2 reduces the binding affinity of CaM to RyR2, thereby causing the spontaneous Ca^<2+> release events in diseased hearts. Correction of the defective CaM binding may be a new strategy to protect against the aberrant Ca^<2+> release in heart failure and lethal arrhythmia.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (27 results)

All 2011 2010 2009 2008 Other

All Journal Article (16 results) (of which Peer Reviewed: 12 results) Presentation (10 results) Remarks (1 results)

  • [Journal Article] Urinary 8-hydroxy-2'-deoxyguanosine reflects symptomatic status and severity of systolic dysfunction in patients with chronic heart failure.2011

    • Author(s)
      Kobayashi S, Susa T, Tanaka T, Wada Y, Okuda S, Doi M, Nao T, Yoshiga Y, Yamada J, Okamura T, Ueyama T, Kawamura S, Yano M, Matsuzaki M.
    • Journal Title

      Eur J Heart Fail. 13

      Pages: 29-36

    • Related Report
      2010 Final Research Report
  • [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, inhibits catecholaminergic polymorphic ventricular tachycardia in a RyR2^<R2474S/+> knock-in mouse model.2010

    • Author(s)
      Kobayashi S, Yano M, Uchinoumi H, Suetomi T, Susa T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Yamamoto T, Matsuzaki M.
    • Journal Title

      Circ J. 74

      Pages: 2579-2584

    • NAID

      10027424202

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure.2010

    • Author(s)
      Ono M, Yano M, Hino A, Suetomi T, Xu X, Susa T, Uchinoumi H, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M.
    • Journal Title

      Cardiovasc Res. 87(4)

      Pages: 609-617

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction.2010

    • Author(s)
      Xu X, Yano M, Uchinoumi H, Hino A, Suetomi T, Ono M, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Ikeda Y, Ikemoto N, Matsuzaki M.
    • Journal Title

      Biochem Biophys Res Commun. 394

      Pages: 660-666

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor.2010

    • Author(s)
      Uchinoumi H, Yano M, Suetomi T, Ono M, Xu X, Tateishi H, Oda T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
    • Journal Title

      Circ Res. 106

      Pages: 1413-1424

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polymorphic Ventricular Tachycardia Is Caused by Mutation-Linked Defective Conformational Regulation of the Ryanodine Receptor.2010

    • Author(s)
      Hitoshi Uchinoumi
    • Journal Title

      Circulation Research

      Volume: 106 Pages: 1413-1424

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction.2010

    • Author(s)
      Xiaojuan Xu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 394 Pages: 660-666

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure.2010

    • Author(s)
      Makoto Ono
    • Journal Title

      Cardiovascular Research

      Volume: 87 Pages: 609-617

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dantrolene, a Therapeutic Agent for Malignant Hyperthermia, Inhibits Catecholaminergic Polymorphic Ventricular Tachycardia in a RyR2(R2474S/+)Knock-In Mouse Model.2010

    • Author(s)
      Shigeki Kobayashi
    • Journal Title

      Circulation Journal

      Volume: 74 Pages: 2579-2584

    • NAID

      10027424202

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor.2009

    • Author(s)
      Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M.
    • Journal Title

      J Am Coll Cardiol. 53

      Pages: 1993-2005

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of ryanodine receptor as a Ca(2+) regulatory center in normal and failing hearts.2009

    • Author(s)
      Yano M, Yamamoto T, Kobayashi S, Matsuzaki M.
    • Journal Title

      J Cardiol. 53 Review

      Pages: 1-7

    • NAID

      10025182309

    • Related Report
      2010 Final Research Report
  • [Journal Article] Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca2+ leak in failing hearts.2009

    • Author(s)
      Tateishi H, Yano M, Mochizuki M, Suetomi T, Ono M, Xu X, Uchinoumi H, Okuda S, Oda T, Kobayashi S, Yamamoto T, Ikeda Y, Ohkusa T, Ikemoto N, Matsuzaki M.
    • Journal Title

      Cardiovasc Res. 81

      Pages: 536-545

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor.2009

    • Author(s)
      Shigeki Kobayashi
    • Journal Title

      Journal of American College of Cardiology 53

      Pages: 1993-2005

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca2+ leak in failing hearts.2009

    • Author(s)
      Hiroki Tateishi
    • Journal Title

      Cardiovascular Research 81

      Pages: 536-45

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective Ca2+ cycling as a key pathogenic mechanism of heart failure.2008

    • Author(s)
      Yano M, Yamamoto T, Kobayashi S, Ikeda Y, Matsuzaki M.
    • Journal Title

      Circ J. 72 Suppl A Review

    • NAID

      110006935628

    • Related Report
      2010 Final Research Report
  • [Journal Article] Role of ryanodine receptor as a Ca(2+) regulatory center innormal and failing hearts.2008

    • Author(s)
      Masafumi Yano
    • Journal Title

      Journal of Cardiology 53

      Pages: 1-7

    • Related Report
      2008 Annual Research Report
  • [Presentation] Mutation-linked Defective Domain Interaction within the Ryanodine Receptor Causes Ca2+ Leak Leading to Catecholaminergic Polymorphic Ventricular Tachycardia2010

    • Author(s)
      Takeshi Suetomi
    • Organizer
      American Heart Association, Scientific sessions 2010
    • Place of Presentation
      Chicago
    • Year and Date
      2010-11-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Correction of Defective Calmodulin Binding to Cardiac Ryanodine Receptor Inhibits Aberrant Ca2+ Release in CPVT-associated Mutation2010

    • Author(s)
      Masakazu Fukuda
    • Organizer
      American Heart Association, Scientific sessions 2010
    • Place of Presentation
      Chicago
    • Year and Date
      2010-11-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Increased Affinity of Calmodulin Binding to Cardiac Ryanodine Receptor Corrects the Defective Channel Gating in Failing Hearts2010

    • Author(s)
      Akihiko Hino
    • Organizer
      American Heart Association, Scientific sessions 2010
    • Place of Presentation
      Chicago
    • Year and Date
      2010-11-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Interruption of Novel Inter-domain Interaction Within RyR2 as a Common Therapeutic Target by Channel Stabilization in Heart Failure and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)2010

    • Author(s)
      Takeshi Yamamoto
    • Organizer
      American Heart Association, Scientific sessions 2010
    • Place of Presentation
      Chicago
    • Year and Date
      2010-11-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] A genetically modified mouse model to better understand catecholaminergic polymorphic ventricular tachycardia. (symposium)2009

    • Author(s)
      Yano M.
    • Organizer
      ESC congress.
    • Place of Presentation
      Barcelona, Spain.
    • Related Report
      2010 Final Research Report
  • [Presentation] Ryanodine Receptor Defects in Heart Failure and Lethal Arrhythmia2009

    • Author(s)
      Yano M.
    • Organizer
      Basic Cardiovascular Sciences Conference (American Heart Association)
    • Place of Presentation
      Las Vegas, Nevada, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] A genetically modified mouse model to better understand catecholaminergic Polymorphic Ventricular Tachycardia2009

    • Author(s)
      Masafumi Yano
    • Organizer
      European Society of Cardiology Congress 2009, Barcelona, 2009. 8
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2009 Annual Research Report
  • [Presentation] A genetically modified mouse model to better understand catecholaminergic Polymorphic Ventricular Tachycardia2009

    • Author(s)
      Masafumi Yano
    • Organizer
      Basic Cardiovascular Sciences Annual Conference (American Heart Association) 2009
    • Place of Presentation
      Las Vegas, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Abnormal Ryanodine Receptor Function in Heart Failure.2008

    • Author(s)
      Yano M.
    • Organizer
      Basic Cardiovascular Sciences Conference (American Heart Association)
    • Place of Presentation
      Keystone, Co, USA
    • Year and Date
      2008-07-30
    • Related Report
      2010 Final Research Report
  • [Presentation] Abnormal Ryanodine Receptor Function in Heart Failure.2008

    • Author(s)
      Masafumi Yano
    • Organizer
      Basic Cardiovascular Sciences Conference 2008 (American Heart Association)
    • Place of Presentation
      Keystone, Co, USA
    • Year and Date
      2008-07-30
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等 なし

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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