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Molecular pathogenetic mechanism of idiopathic cardiomyopathy

Research Project

Project/Area Number 20790520
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

ARIMURA Takuro  Tokyo Medical and Dental University, 難治疾患研究所, 助教 (50342887)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords特発性心筋症 / 肥大型心筋症 / 拡張型心筋症 / 遺伝子変異 / CARP / フクチン / PGM1 / ZASP / Cypher / 心筋Z帯 / 細胞ストレス / ラミンA / C / テストステロン / 心不全
Research Abstract

Idiopathic cardiomyopathy (ICM) is heterogeneous myocardial disease associated with functional abnormalities of cardiomyocytes. The aim of this study was to investigate the novel molecular pathogenesis of ICM caused by the genetic abnormalities. As the results, it was identified that (1) mutations in genes encoding CARP and Fukutin are associated with dilated cardiomyopathy (DCM), and (2)ZASP/Cypher anchors PGM1 to Z-disc under conditions of stress and the impaired binding of PGM1 to ZASP/Cypher might be involved in the pathogenesis of DCM.

Report

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

    (39 results)

All 2010 2009 2008 Other

All Journal Article (21 results) (of which Peer Reviewed: 12 results) Presentation (14 results) Remarks (4 results)

  • [Journal Article] A novel protein found in the I bands of myofibrils is produced by alternative splicing of the DLST gene.2010

    • Author(s)
      Matuda S, Arimura T, Kimura A, Takekura H, Ohta S, Nakano K
    • Journal Title

      Biochim. Biophys. Acta 1800(1)

      Pages: 31-9

    • Related Report
      2009 Final Research Report
  • [Journal Article] Novel mechanisms of trafficking defect caused by KCNQ1 mutations found in long QT syndrome.2009

    • Author(s)
      Sato A, Arimura T, Makita N, Ishikawa T, Aizawa Y, Ushinohama H, Aizawa Y, Kimura A
    • Journal Title

      J. Biol. Chem. 284(50)

      Pages: 35122-33

    • Related Report
      2009 Final Research Report
  • [Journal Article] Megakaryoblastic leukemia factor-1gene in the susceptibility to coronary artery disease.2009

    • Author(s)
      Hinohara K, Nakajima T, Yasunami M, Houda S, Sasaoka T, Yamamoto K, Lee BS, Shibata H, Takahashi TY, Arimura T, Sato A, Naruse T, Ban J, Inoko H, Yamada Y, Sawabe M, Park JE, Izumi T, Kimura A
    • Journal Title

      Hum. Genet. 126(4)

      Pages: 539-47

    • Related Report
      2009 Final Research Report
  • [Journal Article] Autophagic degradation of nuclear components in mammalian cells.2009

    • Author(s)
      Park YE, Hayashi YK, Bonne G, Arimura T, Noguchi S, Nonaka I, Nishino I
    • Journal Title

      Autophagy 5(6)

      Pages: 795-804

    • Related Report
      2009 Final Research Report
  • [Journal Article] Cardiac ankyrin repeat protein gene (ANKRD1) mutations in hypertrophic cardiomyopathy.2009

    • Author(s)
      Arimura T, Bos JM, Sato A, Kubo T, Okamoto H, Nishi H, Harada H, Koga Y, Moulik M, Doi YL, Towbin JA, Ackerman MJ, Kimura A
    • Journal Title

      J. Am. Coll. Cardiol 54(4)

      Pages: 334-42

    • Related Report
      2009 Final Research Report
  • [Journal Article] ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene.2009

    • Author(s)
      Moulik M, Vatta M, Witt SH, Arola AM, Murphy RT, McKenna WJ, Boriek A, Oka K, Labeit S, Bowles NE, Arimura T, Kimura A, Towbin JA
    • Journal Title

      J. Am. Coll. Cardiol 54(4)

      Pages: 325-33

    • Related Report
      2009 Final Research Report
  • [Journal Article] Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy.2009

    • Author(s)
      Arimura T, Inagaki N, Hayashi T, Shichi D, Sato A, Hinohara K, Vatta M, Towbin JA, Chikamori T, Yamashina A, Kimura A
    • Journal Title

      Cardiovasc. Res. 83(1)

      Pages: 80-8

    • Related Report
      2009 Final Research Report
  • [Journal Article] Mutational analysis of fukutin gene in dilated cardiomyopathy and hypertrophic cardiomyopathy.2009

    • Author(s)
      Arimura T, Hayashi YK, Murakami T, Oya Y, Funabe S, Arikawa EH, Hattori N, Nishino I, Kimura A
    • Journal Title

      Circ. J. 73(1)

      Pages: 158-61

    • NAID

      110007007967

    • Related Report
      2009 Final Research Report
  • [Journal Article] Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy2009

    • Author(s)
      Arimura T, et al.
    • Journal Title

      Cardiovasc.Res. 83(1)

      Pages: 80-88

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ANKRD1, the gene encoding cardiac ankyrin repeat protein, is a novel dilated cardiomyopathy gene2009

    • Author(s)
      Moulik M, et al.
    • Journal Title

      J.Am.Coll.Cardiol. 54(4)

      Pages: 325-333

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac ankyrin repeat protein gene(ANKRD1)mutations in hypertrophic cardiomyopathy2009

    • Author(s)
      Arimura T, et al.
    • Journal Title

      J.Am.Coll.Cardiol. 54(4)

      Pages: 334-342

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagic degradation of nuclear components in mammalian cells2009

    • Author(s)
      Park YE, et al.
    • Journal Title

      Autophagy 5(6)

      Pages: 795-804

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Megakaryoblastic leukemia factor-lgene in the susceptibility to coronary artery disease2009

    • Author(s)
      Hinohara K, et al.
    • Journal Title

      Hum.Genet. 126(4)

      Pages: 539-547

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel mechanisms of trafficking defect caused by KCNQ1 mutations found in long QT syndrome2009

    • Author(s)
      Sato A, et al.
    • Journal Title

      J.Biol.Chem. 284(50)

      Pages: 35122-35133

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel protein found in the I bands of myofibrils is produced by alternative splicing of the DLST gene2009

    • Author(s)
      Matsuda S, et al.
    • Journal Title

      Biochim.Biophys.Acta 1800(1)

      Pages: 31-39

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations.2008

    • Author(s)
      Hinohara K, Nakajima T, Takahashi M, Hohda S, Sasaoka T, Nakahara K, Chida K, Sawabe M, Arimura T, Sato A, Lee BS, Ban JM, Yasunami M, Park JE, Izumi T, Kimura A
    • Journal Title

      J. Hum. Genet 53(4)

      Pages: 357-9

    • NAID

      10021248678

    • Related Report
      2009 Final Research Report
  • [Journal Article] Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations2008

    • Author(s)
      Hinohara K, et.al.
    • Journal Title

      J. Hum. Genet 53

      Pages: 357-9

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutational analysis of fukutin gene in dilated cardiomyopathy and hypertrophic cardiomyopathy2008

    • Author(s)
      Arimura T, et.al.
    • Journal Title

      Circ. J. 73

      Pages: 158-61

    • NAID

      110007007967

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improvement of left ventricular dysfunction and survival prognosis of dilated cardiomyopathy by administration of calcium sensitizer SCH00013 in a mouse model

    • Author(s)
      Arimura T, et al.
    • Journal Title

      J.Am.Coll.Cardiol. (In Press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac ankyrin repeat protein gene (ANKRDI) mutations in hypertrophic cardiomyopathy

    • Author(s)
      Arimura T, et.al.
    • Journal Title

      J. Am. Coll. Cardiol (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ANKRDI-the gene encoding cardiac ankyrin repeat protein- is a novel dilated cardiomyopathy gene

    • Author(s)
      Moulik M, et.al.
    • Journal Title

      J. Am. Coll. Cardiol (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Improvement of Left Ventricular Dysfunction and Survival Prognosis of Dilated Cardiomyopathy by Administration of a Novel Calcium Sensitizer in a Mouse Model.2009

    • Author(s)
      Arimura T
    • Organizer
      The 12th Cardiovascular Genomics and Atherosclerosis Symposium Satellite Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2009-10-17
    • Related Report
      2009 Final Research Report
  • [Presentation] Improvement of Left Ventricular Dysfunction and Survival Prognosis of Dilated Cardiomyopathy by Administration of a Novel Calcium Sensitizer in a Mouse Model2009

    • Author(s)
      有村卓朗, et al.
    • Organizer
      The 12^<th> Cardiovascular Genomics and Atherosclerosis Symposium Satellite Meeting
    • Place of Presentation
      韓国・サムソンメディカルセンター
    • Year and Date
      2009-10-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] テストステロンはラミンA/C遺伝子変異LmnaH222P/H222Pマウスにおける拡張型心筋症を増悪させる2009

    • Author(s)
      有村卓朗、木村彰方
    • Organizer
      第54回日本人類遺伝学会
    • Place of Presentation
      東京
    • Year and Date
      2009-09-24
    • Related Report
      2009 Final Research Report
  • [Presentation] テストステロンはラミンA/C遺伝子変異 Lmna^<H222P/H222P>マウスにおける拡張型心筋症を増悪させる2009

    • Author(s)
      有村卓朗, et al.
    • Organizer
      第54回日本人類遺伝学会
    • Place of Presentation
      グランドプリンスホテル高輪
    • Year and Date
      2009-09-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification of Novel Disease Genes for Hypertrophic Cardiomyopathy.2009

    • Author(s)
      Arimura T
    • Organizer
      The 8th Japanese-French Muscular Dystrophy Workshop "Physiopathology to Biotherapy"
    • Place of Presentation
      Paris, France
    • Year and Date
      2009-07-03
    • Related Report
      2009 Final Research Report
  • [Presentation] Identification of Novel Disease Genes for Hypertrophic Cardiomyopathy2009

    • Author(s)
      有村卓朗, et al.
    • Organizer
      The 8^<th> Japanese-French Muscular Dystrophy Workshop
    • Place of Presentation
      フランス・ピティエサルペトリエール病院
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification of a novel gene for hypertrophic cardiomyopathy.2009

    • Author(s)
      Arimura T, Bos JM, Sato A, Kubo T, Okamoto H, Nishi H, Harada H, Koga Y, Doi YL, Ackerman MJ, Kimura A
    • Organizer
      The 73th Annual Meeting of the Japanese Circulation Society
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2009-03-22
    • Related Report
      2009 Final Research Report
  • [Presentation] Identification of a novel gene for hypertrophic cardiomyopathy2009

    • Author(s)
      Arimura T, et.al.
    • Organizer
      The 73^<th> Annual Meeting of the Japanese Circulation Society
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2009-03-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] 特発性心筋症モデルマウスの作製とその病態解析-ヒトからマウスへ、マウスからヒトへ-2008

    • Author(s)
      有村卓朗
    • Organizer
      第30回心筋生検研究会ミニシンポジウム
    • Place of Presentation
      津
    • Year and Date
      2008-11-28
    • Related Report
      2009 Final Research Report
  • [Presentation] 特発性心筋症モデルマウスの作製とその病態解析-ヒトからマウスへ、マウスからヒトへ-2008

    • Author(s)
      有村卓朗,et.al.
    • Organizer
      第30回心筋生検研究会ミニシンポジウム
    • Place of Presentation
      三重大学
    • Year and Date
      2008-11-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] Identification of Novel Disease Genes for Hereditary Cardiomyopathy.2008

    • Author(s)
      Arimura T
    • Organizer
      The 11th Cardiovascular Genomics and Atherosclerosis Symposium Satellite Meeting
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2008-11-01
    • Related Report
      2009 Final Research Report
  • [Presentation] Identification of Novel Disease Genes for Hereditary Cardiomyopathy2008

    • Author(s)
      Arimura T, et.al.
    • Organizer
      The 11^<th> Cardiovascular Genomics and Atherosclerosis Symposium Satellite Meeting
    • Place of Presentation
      韓国・サムソンメディカルセンター
    • Year and Date
      2008-11-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] CARPおよびタイチンN2A領域内変異は肥大型心筋症を引き起こす2008

    • Author(s)
      有村卓朗、佐藤光希、久保亨、岡本洋、西 宏文、原田晴仁、古賀義則、土居義典、木村彰方
    • Organizer
      第53回日本人類遺伝学会
    • Place of Presentation
      横浜
    • Year and Date
      2008-09-28
    • Related Report
      2009 Final Research Report
  • [Presentation] CARPおよびタイチンN2A領域内変異は肥大型心筋症を引き起こす2008

    • Author(s)
      有村卓朗, et.al.
    • Organizer
      第53回日本人類遺伝学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-09-28
    • Related Report
      2008 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

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

    • Related Report
      2009 Final Research Report
  • [Remarks] 「肥大型心筋症の新たな原因遺伝子を発見」-心臓肥大の新たなメカニズムの解明で治療法の開発に道-

    • URL

      http://www.tmd.ac.jp/cmn/soumu/kouhou/news20090710.html

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2008 Annual Research Report

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

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