• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2012 Fiscal Year Final Research Report

Development of strategies for handling heart failure based on the molecular pathogenesis of cardiomyopathy

Research Project

  • PDF
Project/Area Number 22390157
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KIMURA Akinori  東京医科歯科大学, 難治疾患研究所, 教授 (60161551)

Project Period (FY) 2010 – 2012
Keywords遺伝学 / 遺伝子 / ゲノム / 循環器・高血圧
Research Abstract

Identification of novel disease genes for cardiomyopathy and functional analyses of various cardiomyopathy-associated mutations were performed. We identified novel disease genes for cardiomyopathy, such that CARP mutations in hypertrophic cardiomyopathy, nebulette mutations and BAG3 in dilated cardiomyopathy,and myopalladin mutations in hypertrophic cardiomyopathy, dilated cardiomyopathy and restrictive cardiomyopathy. Functional studies of the cardiomyopathy-associated mutations revealed that CARP mutations increased binding to titin and enhance the nuclear translocation. Nebulette mutations impaired sarcomerogenesis and BAG3 mutations increased susceptibility to stress-induced apoptosis. Myopalladin mutations impaired sarcomerogenesis. In addition, we revealed a molecular mechanism for calcium sensitivity of cardiac contraction by heart-specific small subunit of myosin phosphatase, M21.Moreover, it was demonstrated that a chemical enhancing calcium sensitivity of muscle contraction, SCH00013, could prolong the survival prognosis of dilated cardiomyopathy in lamina/C mutation knock-in mice, suggesting that the regulation of calcium sensitivity is a novel therapeutic/preventive strategy for heart failure associated with cardiomyopathy

  • Research Products

    (44 results)

All 2013 2012 2011 2010 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (24 results) Remarks (1 results)

  • [Journal Article] Novel SCN3B mutation associated with Brugada syndrome affects intracellular trafficking and function of Nav1.52013

    • Author(s)
      Ishikawa T, Takahashi N, Ohno S, Sakurada H, Nakamura K, On YK, Park JE, Makiyama T, Horie M, Arimura T, Makita N, Kimura A
    • Journal Title

      Circ J

      Volume: 77(4) Pages: 959-967

    • Peer Reviewed
  • [Journal Article] Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy2012

    • Author(s)
      Otsuka H, #Arimura T, Abe T, Kawai H, Aizawa Y, Kubo T, Kitaoka H, Nakamura H, Nakamura K, Okamoto H, Ichida F, Ayusawa M, Nunoda S, Isobe M, Matsuzaki M, Doi YL, Fukuda K, Sasaoka T, Izumi T, Ashizawa N, Kimura A
    • Journal Title

      Circ J

      Volume: 76(2) Pages: 453-461

    • Peer Reviewed
  • [Journal Article] Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations2012

    • Author(s)
      Purevjav E, Arimura T, Augustin S, Huby A-C, Takagi K, Nunoda S, Kearney DL, Taylor MD, Terasaki F, Bos JM, Ommen SR, Shibata H, Takahashi M, Itoh-Satoh M, McKenna W, Murphy RT, Labeit S, Yamanaka Y, Machida N, Park JE, Alexander PMA, Weintraub RG, Kitaura Y, Ackerman MJ, Kimura A, Towbin JA
    • Journal Title

      Hum Mol Genet

      Volume: 21(9) Pages: 2039-2053

    • Peer Reviewed
  • [Journal Article] Similarities and differences in genetic and clinical characteristics between early repolarization syndrome and Brugada syndrome2012

    • Author(s)
      Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Sato M, Hosaka Y, Fukae S, Chinushi M, Oda H, Okabe H, Kimura A, Maemura K, Watanabe I, Kamakura S, Aizawa Y, Shimizu W, Makita N
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 5(2) Pages: e60-e61

    • Peer Reviewed
  • [Journal Article] Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization2012

    • Author(s)
      Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Makiyama T, Nagao S, Yagihara N, Takehara N, Kawamura Y, Sato A, Okamura K, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Shimizu W, Makita N
    • Journal Title

      Int J Cardiol

      Volume: 159(3) Pages: 238-240

    • Peer Reviewed
  • [Journal Article] Loss-of-function of hNav1.5 by ZASP1-D117N associated with intraventricular conduction disturbances in left ventricular noncompaction2012

    • Author(s)
      Xi Y, Ai T, De Lange E, Li Z, Wu G, Brunelli L, Kyle WB, Cheng J, Ackerman MJ, Kimura A, Weiss JN, Qu Z, Kim JJ, Faulkner G, Vatta M
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 5(5) Pages: 1017-1026

    • Peer Reviewed
  • [Journal Article] Dilated phase of hypertrophic cardiomyopathy caused by two different sarcomere mutations, treated with surgical left ventricular reconstruction and cardiac resynchronization therapy with a defibrillator2012

    • Author(s)
      Sato A, Sakamoto N, Ando K, Kaneshiro T, Uekita H, Sugimoto K, Yamaki T, Kunii H, Nakazato K, Suzuki H, Saitoh S, Sato M, Tamagawa K, Arimura T, Kimura A, Takeishi Y
    • Journal Title

      Intern Med

      Volume: 51(18) Pages: 2559-2564

    • Peer Reviewed
  • [Journal Article] A novel disease gene for Brugada syndrome: sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.52012

    • Author(s)
      Ishikawa T, Sato A, Marcou CA, Tester DJ, Ackerman MJ, Crotti L, Schwartz PJ, On YK, Park JE, Nakamura K, Hiraoka M, Nakazawa K, Sakurada H, Arimura T, Makita N, Kimura A
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 5(6) Pages: 1098-1107

    • Peer Reviewed
  • [Journal Article] Contribution of genetic factors to the pathogenesis of dilated cardiomyopathy: the cause of dilated cardiomyopathy: genetic or acquired?(genetic-side)2011

    • Author(s)
      Kimura A
    • Journal Title

      Circ J

      Volume: 75(7) Pages: 1756-1765

    • Peer Reviewed
  • [Journal Article] Genetic screening and double mutation in Japanese patients with hypertrophic cardiomyopathy2011

    • Author(s)
      Kubo T, Kitaoka H, Okawa M, Baba Y,Hirota T,Hayato K, Yamasaki N,Matsumura Y, Otsuka H,Arimura T,Kimura A, Doi YL
    • Journal Title

      Circ J

      Volume: 75(11) Pages: 2654-2659

    • Peer Reviewed
  • [Journal Article] Dilated cardiomyopathy-associated BAG3 mutations impair the Z-disc assembly and enhance the sensitivity to apoptosis in cardiomyocytes2011

    • Author(s)
      Arimura T, Ishikawa T, Nunoda S, Kawai S,Kimura A
    • Journal Title

      Hum Mutat

      Volume: 32(12) Pages: 1481-1491

    • Peer Reviewed
  • [Journal Article] Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization2011

    • Author(s)
      Watanabe H, Nogami A, Ohkubo K, Kawata H, Hayashi Y, Ishikawa T, Nagao S,Yagihara N, Takehara N, Kawamura Y,Sato A, Okamura K, Sato M, Hosaka Y,Fukae S, Chinushi M, Oda H, Okabe H, Kimura A, Maemura K, Watanabe I,Kamakura S,Aizawa Y, Shimizu W, Makita N
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 4(6) Pages: 874-881

    • Peer Reviewed
  • [Journal Article] A ZASP missense mutation, S196L, leads to cytoskeletal and electrical abnormalities in a mouse model of cardiomyopathy2010

    • Author(s)
      Li Z, Ai T, Samani K, Xi Y, Tzeng HP,Xie M,Wu S, Ge S, Taylor MD, Dong JW,Cheng J, Ackerman MJ, Kimura A, Sinagra G, Brunelli L, Faulkner G, Vatta M
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 3(6) Pages: 646-656

    • Peer Reviewed
  • [Journal Article] A frameshift deletion mutation in the cardiac myosin-binding protein C gene was associated with dilated phase of hypertrophic cardiomyopathy and dilated cardiomyopathy2010

    • Author(s)
      Hitomi N, Kubo T, Kitaoka H, Hirota T,Hamada T, Hoshikawa E, Hayato K, Okawa M, Kimura A, Doi YL
    • Journal Title

      J Cardiol

      Volume: 56(2) Pages: 189-196

    • Peer Reviewed
  • [Journal Article] Nebulette mutations are associated with dilated cardiomyopathy and endocardial fibroelastosis2010

    • Author(s)
      Purevjav E, Varela J, Morgado M,Kearney DL, Li H, Taylor MD, Arimura T, Moncman CL, McKenna W, Labeit S, Vatta M, Bowles NE, Kimura A, Boriek AM, Towbin JA
    • Journal Title

      J Am Coll Cardiol

      Volume: 56(18) Pages: 1493-1502

    • Peer Reviewed
  • [Journal Article] Heart-specific small subunit of myosin light chain phosphatase activates Rho-associated kinase and regulates phosphorylation of myosin phosphatase target subunit 12010

    • Author(s)
      Shichi D, Arimura T, Ishikawa T, Kimura A
    • Journal Title

      J Biol Chem

      Volume: 285(44) Pages: 33680-33690

    • Peer Reviewed
  • [Journal Article] A ZASP missense mutation, S196L,leads to cytoskeletal and electrical abnormalities in a mouse model of cardiomyopathy2010

    • Author(s)
      Li Z, Ai T, Samani K, Xi Y, Tzeng HP,Xie M,Wu S, Ge S, Taylor MD, Dong JW,Cheng J, Ackerman MJ, Kimura A, Sinagra G, Brunelli L, Faulkner G,Vatta M
    • Journal Title

      Circ Arrhythm Electrophysiol

      Volume: 3(6) Pages: 646-656

    • Peer Reviewed
  • [Journal Article] Impact of ANKRD1 mutations associated with hypertrophic cardiomyopathy on contraction parameters of engineered heart tissue

    • Author(s)
      Crocini C, Arimura T, Reischmann S, Eder A, Braren I, Hansen A, Eschenhagen T, Kimura A, Carrier L
    • Journal Title

      Basic Res Cardiol

      Volume: (in press)

    • DOI

      doi:10.1007/s00395-013-0349-x

    • Peer Reviewed
  • [Journal Article] Nuclear accumulation of androgen receptor in gender difference of dilated cardiomyopathy due to lamin A/C mutations

    • Author(s)
      Arimura T, Onoue K, Takahashi-Tanaka Y, Ishikawa T, Kuwahara M, Setou M, Shigenbu S, Yamaguchi K, Bertrand AT, Machida N, Takayama K, Fukusato M, Tanaka R, Somekawa T, Nakano T, Yamane Y, Kuba K, Imai Y, Saito N, Bonne G, Kimura A
    • Journal Title

      Cardiovasc Res

      Volume: (in press)

    • DOI

      doi:10.1093/cvr/cvt106

    • Peer Reviewed
  • [Presentation] 肥大型心筋症および拡張型心筋症におけるタイチンA/M帯変異の意義2012

    • Author(s)
      有村卓朗, 石川泰輔, 木村彰方
    • Organizer
      第57回日本人類遺伝学会
    • Place of Presentation
      東京
    • Year and Date
      2012-10-26
  • [Presentation] ブルガダ症候群患者に見出されたSLMAP変異とその機能解析2012

    • Author(s)
      石川泰輔, 佐藤光希, 有村卓朗, 蒔田直昌, 木村彰方
    • Organizer
      第57回日本人類遺伝学会
    • Place of Presentation
      東京
    • Year and Date
      2012-10-26
  • [Presentation] Impact of testosterone on progression of dilated cardiomyopathy in a Lmna-mutation knock-in mouse model2012

    • Author(s)
      Arimura T, Bonne G, Kimura A
    • Organizer
      The 9th Japanese-French Symposium for "Muscular Dystrophy"
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2012-09-18
  • [Presentation] Dilated cardiomyopathy-associated BAG3 mutations impair the Z-disc assembly and enhance sensitivity to apoptosis in cardiomyocytes2012

    • Author(s)
      Arimura T, Ishikawa T, Nunoda S, Kawai S, Kimura A
    • Organizer
      The 76th Annual Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka,Japan
    • Year and Date
      2012-03-17
  • [Presentation] A novel mechanism of Brugada syndrome:Mutation of sarcolemmal membrane-associated protein (SLMAP) gene impaired hNav1.5 function2012

    • Author(s)
      Ishikawa T, Sato A, Arimura T, Sakurada H, Makita N, Kimura A
    • Organizer
      The 76th Annual Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka, Japan.
    • Year and Date
      2012-03-16
  • [Presentation] Cardiomyopathy as a disease of abnormalities in sensing for stretch and metabolic stress in cardiac sarcomere2012

    • Author(s)
      Kimura A
    • Organizer
      4th Sensing Biology Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2012-01-30
  • [Presentation] Novel molecular mechanisms of idiopathic cardiomyopathy2011

    • Author(s)
      Arimura T, Kimura A
    • Organizer
      第28回国際心臓研究学会日本部会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-12-03
  • [Presentation] 心筋症:遺伝子異常からみた分子病態2011

    • Author(s)
      木村彰方
    • Organizer
      第20回小児心筋疾患学会ランチョンセミナー
    • Place of Presentation
      東京
    • Year and Date
      2011-11-19
  • [Presentation] BAG3変異は心筋細胞のZ帯整合性異常とアポトーシス感受性増強を介して拡張型心筋症を引き起こす2011

    • Author(s)
      有村卓朗, 石川泰輔, 布田伸一, 河合祥雄, 木村彰方
    • Organizer
      第56回日本人類遺伝学会
    • Place of Presentation
      幕張
    • Year and Date
      2011-11-10
  • [Presentation] ブルガダ症候群患者に見出されたSCN3B遺伝子V110I変異とその機能解析2011

    • Author(s)
      石川泰輔, 有村卓朗, 蒔田直昌, 木村彰方
    • Organizer
      第56回日本人類遺伝学会
    • Place of Presentation
      幕張
    • Year and Date
      2011-11-10
  • [Presentation] Coronary artery disease-associated gene MKL1 is involved in the differentiation of macrophage2011

    • Author(s)
      Kimura A, An J, Hinohara K, Nakajima T
    • Organizer
      The 14th Cardiovascular Genomics and Atherosclerosis Symposium
    • Place of Presentation
      Seoul,Korea
    • Year and Date
      2011-10-28
  • [Presentation] Dilated cardiomyopathy-associated BAG3 mutations impair the sarcomere assembly and increase the sensitivity to apoptosis2011

    • Author(s)
      Arimura T, Ishikawa T, Kimura A
    • Organizer
      The 14th Cardiovascular Genomics and Atherosclerosis Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-10-28
  • [Presentation] Role of sarcolemmal membrane-associated protein (SLMAP) gene in Brugada syndrome2011

    • Author(s)
      Ishikawa T, Arimura T, Kimura A
    • Organizer
      The 14th Cardiovascular Genomics and Atherosclerosis Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-10-28
  • [Presentation] Heart-specific Small Subunit of Myosin Light Chain Phosphatase Activates Rho-associated Kinase and Regulates Phosphorylation of Myosin Phosphatase Target Subunit 12011

    • Author(s)
      Arimura T, Kimura A
    • Organizer
      第75回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2011-08-03
  • [Presentation] 心筋症の遺伝子異常と分子病態2011

    • Author(s)
      木村彰方
    • Organizer
      第73回東京心臓の会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-11
  • [Presentation] 新規カルシウム増感剤SCH00013による拡張型心筋症病態の治療効果の検討2010

    • Author(s)
      有村卓朗,木村彰方
    • Organizer
      第55回日本人類遺伝学会
    • Place of Presentation
      大宮
    • Year and Date
      2010-10-30
  • [Presentation] 家族性肥大型心筋症患者における原因遺伝子変異解析2010

    • Author(s)
      大塚春奈,有村卓朗,久保亨,土居義典,木村彰方
    • Organizer
      第55回日本人類遺伝学会
    • Place of Presentation
      大宮
    • Year and Date
      2010-10-28
  • [Presentation] 教育講演心筋症の遺伝子診断2010

    • Author(s)
      木村彰方
    • Organizer
      第14回日本心不全学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-08
  • [Presentation] Heart-specific Small Subunit of Myosin Light Chain Phosphatase Activates Rho-associated Kinase and Regulates Phosphorylation of Myosin Phosphatase Target Subunit 12010

    • Author(s)
      Arimura T, Shichi D, Ishikawa T, Kimura A
    • Organizer
      The 13th Cardiovascular Genomics and Atherosclerosis Symposium Satellite Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2010-10-02
  • [Presentation] Molecular etiology of idiopathic cardiomyopathy2010

    • Author(s)
      Kimura A
    • Organizer
      XXth World ongress of the International Society for Heart Research 2010 Kyoto, Kyoto, Japan
    • Year and Date
      2010-05-14
  • [Presentation] A novel calcium sensitizer, SCH00013, improves left ventricular dysfunction and survival prognosis of dilated cardiomyopathy in a mouse model2010

    • Author(s)
      Arimura T, Kimura A
    • Organizer
      XXth World Congress of the International Society for Heart Research 2010 Kyoto
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-05-14
  • [Presentation] Cardiac ankyrin repeat protein gene (ANKRD1) mutations in hypertrophic cardiomyopathy2010

    • Author(s)
      Arimura T, Kimura A
    • Organizer
      XXth World Congress of the International Society for Heart Research 2010 Kyoto
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-05-13
  • [Presentation] Novel mechanisms of trafficking defect caused by KCNQ1 mutations found in long QT syndrome2010

    • Author(s)
      Ishikawa T, Arimura T, Sato A, Makita N, Aizawa Y, Ushinohama H, Aizawa Y, Kimura A
    • Organizer
      XXth World Congress of the International Society for Heart Research 2010 Kyoto
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-05-13
  • [Presentation] Plenary session Cardiomyopathy UP to DATE. Molecular basis of cardiomypathies: recent advances2010

    • Author(s)
      Kimura A
    • Organizer
      The 74th annual scientific meeting of the Japanese Circulation Society
    • Place of Presentation
      Kyoto
    • Year and Date
      2010-03-06
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/mri/mri-mpath/index_j.html

URL: 

Published: 2014-08-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi