Molecular pathogenetic mechanism of idiopathic cardiomyopathy

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790520
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Tokyo 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
• 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

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.

Research Products

• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Remarks] 研究室ホームページ
  • URL: http://www.tmd.ac.jp/mri/mri-mpath/index_j.html
• [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