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Arrhythmogenic gap junction remodeling in diseased hearts

Research Project

Project/Area Number 15K09078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionNagoya University

Principal Investigator

Honjo Haruo  名古屋大学, 環境医学研究所, 准教授 (70262912)

Co-Investigator(Kenkyū-buntansha) 辻 幸臣  長崎大学, 医歯薬学総合研究科(医学系), 講師 (60432217)
山崎 正俊  東京大学, 大学院工学系研究科(工学部), 特任研究員 (30627328)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords不整脈 / ギャップ結合 / 心臓電気生理学 / 活動電位 / イオンチャネル / 心臓電気生理 / 電気生理学
Outline of Final Research Achievements

Arrhythmogenic remodeling of myocardial gap junctions was investigated using a transgenic mouse model with cardiac dysfunction/lethal ventricular arrhythmias, and a rabbit electrical storm model induced by sustained severe bradycardia. In diseased hearts, connexin43 expression was decreased in the intercalated disc region of ventricular myocytes, which was associated with a reduction of conduction velocity and an increase in the spatial heterogeneity of action potential repolarization, leading to increased susceptibility of reentrant ventricular tachyarrhythmias. In addition, the results suggested that the renin-angiotensin system and calmodulin/CAMKII are involved in arrhythmogenic gap junction remodeling in diseased hearts.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (31 results)

All 2018 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (24 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results)

  • [Journal Article] Interaction of Phase Singularities on Spiral Wave Tail: Reconsideration of Caputuring Excitable Gap.2018

    • Author(s)
      Tomii N, Yamazaki M, Arafune T, Kamiya K, Nakazawa K, Honjo H, Shibata N, Sakuma I.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: in press Issue: 2 Pages: 318-326

    • DOI

      10.1152/ajpheart.00558.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ranolazine Facilitates Termination of Ventricular Tachyarrhythmia Associated With Acute Myocardial Ischemia Through Suppression of Late <b><i>I</i></b><sub>Na</sub>-Mediated Focal Activity2017

    • Author(s)
      Ogawa T, Honjo H, Yamazaki M, Kushiyama Y, Sakuma I, Kodama I, Kamiya K.
    • Journal Title

      Circulation Journal

      Volume: 81 Issue: 10 Pages: 1411-1428

    • DOI

      10.1253/circj.CJ-17-0128

    • NAID

      130006099889

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles2016

    • Author(s)
      Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
    • Journal Title

      American Journal of Physiology Heart and Circulatory Physiology

      Volume: 311 Issue: 1 Pages: 750-758

    • DOI

      10.1038/srep34198

    • NAID

      120005946586

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Calmodulin/CaMK II inhibition improves intercellular communication and impulse propagation in the heart, and is anti-arrhythmic under conditions when fibrosis is absent2016

    • Author(s)
      Takanari H, Bourqonje VJ, Fontes MS, Raaijmakers AJ, Driessen H, Jansen JA, van der Nagel R, Kok B, van Stuijvenberg L, Boulaksil M, Takemoto Y, Yamazaki M, Tsuji Y, Honjo H, Kamiya K. Kodama I, Anderson ME, van der Heyden MA, van Rijen HV, van Veen TA, Vos MA
    • Journal Title

      Cardiovascular Research

      Volume: 111 Issue: 4 Pages: 410-421

    • DOI

      10.1093/cvr/cvw173

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The renin-angiotensin system promotes arrhythmogenic substrates andalethal arrhythmias in mice with non-ischemic cardiomyopathy2016

    • Author(s)
      Yamada C, Kuwahara K, Yamazaki M, Nakagawa Y, Nishikimi T, Kinoshita H, Kuwabara Y, Minami T, Yamada Y, Shibata J, Nakao K, , Arai Y, Honjo H, Kamiya K, Nakao K, Kimura T
    • Journal Title

      Cardiovascular Research

      Volume: 109 Issue: 1 Pages: 162-173

    • DOI

      10.1093/cvr/cvv248

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection Algorithm of Phase Singularity Using Phase Variance Analysis for Epicardial Optical Mapping Data2015

    • Author(s)
      Naoki Tomii, Masatoshi Yamazaki, Tatsuhiko Arafune, Haruo Honjo, Nitaro Shibata, and Ichiro Sakuma
    • Journal Title

      IEEE transactions on bio-medical engineering

      Volume: Vol.PP Issue: 9 Pages: 1795-1803

    • DOI

      10.1109/tbme.2015.2502726

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanisms of Cardiac Impulse Propagation and Arrhythmogenesis2015

    • Author(s)
      本荘晴朗
    • Journal Title

      Transactions of Japanese Society for Medical and Biological Engineering

      Volume: 53 Issue: 3 Pages: 123-129

    • DOI

      10.11239/jsmbe.53.123

    • NAID

      130005106896

    • ISSN
      1347-443X, 1881-4379
    • Related Report
      2015 Research-status Report
    • Open Access
  • [Presentation] Novel panoramic endocardial optical mapping reveals a role of the superior vena cava in the maintenance of atrial fibrillation2017

    • Author(s)
      Takemoto Y, Yamazaki M, Honjo H, Murohara T
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      石川県立音楽堂他, 金沢市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Effects of stretch-activated channel and Ca2+/calmodulin-dependent protein kinase II on atrial fibrillation2017

    • Author(s)
      植田典浩, 小川貴史, 竹本芳雄, 櫛山泰規, 丹羽良子, 山崎正俊, 本荘晴朗, 神谷香一郎
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      石川県立音楽堂他, 金沢市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Computer simulation study of low energy defibrillation by multiple point stimuli2017

    • Author(s)
      Tomii N, Yamazaki M, Honjo H, Kamiya K, Shibata N, Sakuma I
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Accumulated phase variance analysis of cardiac spiral wave dynamics2017

    • Author(s)
      Seno H, Tomii N, Yamazaki M, Honjo H, Kamiya K, Shibata N, Sakuma I
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the current stimulus phenomenon in the ventricle film by optical measurement.2017

    • Author(s)
      Monma M, Yatabe J, Tomii N, Shibata N, Yamazaki M, Honjo H, Arafune T
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The derivation method of cardiac fiber direction using virtual electrode polarization.2017

    • Author(s)
      Yatabe J, Tomii N, Shibata, Yamazaki M, Honjo H, Yaguchi T, Arafune T, Honma A.
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Spiral wave reentry in endocardium of ventricle using optical mapping system.2017

    • Author(s)
      Kawashima K, Yatabe J, Tomii N, Shibata N, Yamazaki M, Honjo H, Arafune T, Sakuma I.
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] シミュレーションモデルを用いた点通電刺激によるspiral wave停止プロトコルに関する研究2017

    • Author(s)
      富井直樹, 山崎正俊, 神谷香一郎, 柴田仁太郎, 本荘晴朗, 佐久間一郎
    • Organizer
      第32回心電情報処理ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] 累積位相分散解析を用いた心臓旋回性興奮の挙動解析2017

    • Author(s)
      瀬野宏, 富井直樹, 山崎正俊, 本荘晴朗, 神谷香一郎, 柴田仁太郎, 佐久間一郎
    • Organizer
      第32回心電情報処理ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] Electrical storm associated with bradycardia2017

    • Author(s)
      Tsuji Y
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Therapeutic target of atrial fibrillation2017

    • Author(s)
      Yamazaki M
    • Organizer
      APHRS/JHRS2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Effective point electric stimulation for cardiac spiral wave termination2016

    • Author(s)
      Tomii N, Yamazaki M, Arafune T, Kamiya K, Honjo H, Shibata N, Sakuma I
    • Organizer
      AHA Scientific Sessions 2016
    • Place of Presentation
      Ernest N. Memorial Convention Center, New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
  • [Presentation] Roles of late INa-mediated focal electrical activities in ventricular tachyarrhythmia associated with acute myocardial ischemia2016

    • Author(s)
      Ogawa T, Honjo H, Yamazaki M, Niwa R, Ueda N, Kamiya K
    • Organizer
      ESC Congress 2016
    • Place of Presentation
      Fiera di Rome, Rome, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Research-status Report
  • [Presentation] Simultaneous optical mapping of membrane voltage and intracellular calcium without excitation-contraction uncoupler2016

    • Author(s)
      Tachiyanagi N, Arafune T, Shibata N, Ogawa T, Yamazaki M, Honjo H, Kamiya K, Homma A
    • Organizer
      第63回日本不整脈心電学会学術集会
    • Place of Presentation
      札幌コンベンションセンター, 札幌市
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Phase shift mechanisms of spiral reentry induced by low energy stimulation2016

    • Author(s)
      Yatabe J, Tachiyanagi N, Tomii N, Noguchi H, Shibata N, Ogawa T, Yamazaki M, Honjo H, Arafune T, Homma A
    • Organizer
      第63回日本不整脈心電学会学術集会
    • Place of Presentation
      札幌コンベンションセンター, 札幌市
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Basic concept and clinical implications of phase mapping2016

    • Author(s)
      Arafune T, Sakuma I, Shibata N, Ashihara T, Yamazaki M, Honjo H: Basic concept and clinical implications of phase mapping
    • Organizer
      第63回日本不整脈心電学会学術集会
    • Place of Presentation
      札幌コンベンションセンター, 札幌市
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 3-D atrial scroll wave as a mechanism of persistent atrial fibrillation2016

    • Author(s)
      Yamazaki M, Honjo H, Takemoto Y, Kamiya K, Kalifa J
    • Organizer
      第55回日本生体医工学会大会
    • Place of Presentation
      富山国際会議場, 富山市
    • Year and Date
      2016-04-26
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 位相分散マップによる心臓旋回興奮解析2016

    • Author(s)
      富井直輝, 山﨑正俊, 荒船龍彦, 本荘晴朗, 神谷香一郎, 柴田仁太郎, 佐久間一郎
    • Organizer
      第55回日本生体医工学会大会
    • Place of Presentation
      富山国際会議場, 富山市
    • Year and Date
      2016-04-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 膜電位/Ca2+同時工学マッピングを用いたCa2+バーストの解析2016

    • Author(s)
      立柳紀林, 野口展士, 柴田仁太郎, 山﨑正俊, 本荘晴朗, 荒船龍彦, 本間章彦
    • Organizer
      第55回日本生体医工学会大会
    • Place of Presentation
      富山国際会議場, 富山市
    • Year and Date
      2016-04-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Cardiac excitation wave propagation and arrhythmogenesis2016

    • Author(s)
      Honjo H
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Multi-scale simulation studies of excitation conduction including cardiac conduction systems and whole ventricles2016

    • Author(s)
      Inada S, Harrell DT, Haraguchi R, Ashihara T, Aiba T, Ikeda T, Mitsui K, Honjo H, Nakazawa K
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Spontaneous activity of pulmonary vein myocardial sleeves2015

    • Author(s)
      Honjo H
    • Organizer
      第30回日本巣性脈学会/第32回日本心電学会
    • Place of Presentation
      京都
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Rotors and the dynamics of atrial fibrillation in isolated sheep hearts2015

    • Author(s)
      Yamazaki M, Honjo H, Kodama I, Kamiya K
    • Organizer
      第30回日本巣性脈学会/第32回日本心電学会
    • Place of Presentation
      京都
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Can computer simulation technique contribute regenerative medicine?2015

    • Author(s)
      Inada S, Harrell DT, Haraguchi R, Ashihara T, Aiba T, Ikeda T, Mitsui K, Honjo H, Shibata N, Makita N, Kamiya K, Kodama I, Nakazawa K
    • Organizer
      第30回日本巣性脈学会/第32回日本心電学会
    • Place of Presentation
      京都
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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