Genetic backgrounds of inherited arrhythmias -disease specific human iPS cells-

• Project/Area Number: 23790848
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MAKIYAMA Takeru 京都大学, 医学研究科, 助教 (30528302)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 不整脈 / 分子心臓病態学

Research Abstract

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disorder characterized by adrenergically mediated ventricular tachyarrhythmias which cause syncope and sudden death without structural heart diseases. We generated disease-specific iPS cells from a patient associated with CPVT. The differentiated cardiomyocytes had an increased susceptibility to catecholamine-induced calcium waves. Our results suggest that the differentiated myocytes from the patient could be a useful model of CPVT enabling us to investigate the disease causing mechanisms and develop new therapies.

Research Products

• [Journal Article] Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture (2013)
  • Author(s): Kamakura T, Makiyama T, Sasaki K, Yoshida Y , Wuriyanghai Y, Chen J, Hattori T, Ohno S, Kita T, Horie M, Yamanaka S, Kimura T
  • Journal Title: Circ J
  • NAID: 40020559020
• [Journal Article] Long-Term Follow-Up of a Pediatric Cohort With Short QT Syndrome (2013)
  • Author(s): Villafane J, Atallah J, Gollob MH, Maury P, Wolpert C, Gebauer R, Watanabe H, Horie M, Anttonen O, Kannankeril P, Faulknier B, Bleiz J, Makiyama T, Shimizu W, Hamilton R, Young ML.
  • Journal Title: J Am Coll Cardiol
• [Journal Article] Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture (2013)
  • Author(s): Kamakura T
  • Journal Title: Circ J Volume: 77 Pages: 1307-14
  • Peer Reviewed
• [Journal Article] Long-Term Follow-Up of a Pediatric Cohort With Short QT Syndrome (2013)
  • Author(s): Villafañe J
  • Journal Title: J Am Coll Cardiol Volume: 61 Pages: 1183-91
  • Peer Reviewed
• [Journal Article] Novel SCN3B Mutation Associated With Brugada Syndrome Affects Intracellular Trafficking and Function of Nav1.5 (2012)
  • 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
• [Journal Article] A novel gain-of-function KCNJ2 mutation associated with short QT syndrome impairs inward rectification of Kir2.1 currents. (2012)
  • Author(s): Hattori T, Makiyama T, Akao M, Ehara E, Ohno S, Iguchi M, Nishio Y, Sasaki K, Itoh H, Yokode M, Kita T, Horie M, Kimura T.
  • Journal Title: Cardiovasc Res Volume: 93(4) Pages: 666-73
• [Journal Article] Phenotype variability in patients carrying KCNJ2 mutations (2012)
  • Author(s): Kimura H, Zhou J, Kawamura M, Itoh H, Mizusawa Y, Ding WG, Wu J, Ohno S, Makiyama T, Miyamoto A, Naiki N, Wang Q, Xie Y, Suzuki T, Tateno S, Nakamura Y, Zang WJ, Ito M, Matsuura H, Horie M
  • Journal Title: Circ Cardiovasc Genet Volume: 5(3) Pages: 344-53
• [Journal Article] Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization. (2012)
  • 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, Aizaw
  • Journal Title: Int J Cardiol. Volume: 159(3) Pages: 238-40
• [Journal Article] A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1currents (2012)
  • Author(s): Hattori T, Makiyama T, Akao M, Ehara E, Ohno S, Iguchi M, Nishio Y, Sasaki K, Itoh H, Yokode M, Kita T, Horie M, Kimura T.
  • Journal Title: Cardiovasc Res Volume: 93(4) Pages: 666-73
• [Journal Article] A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. (2012)
  • Author(s): Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W, Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M, Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M.
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 5(1) Pages: 163-72
  • NAID: 120006985450
• [Journal Article] Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population (2012)
  • Author(s): Miyamoto A, Hayashi H, Yoshino T, Kawaguchi T, Taniguchi A, Itoh H, Sugimoto Y, Itoh M, Makiyama T, XueJQ, Murakami Y, Horie M
  • Journal Title: Heart Rhythm. Volume: 9(1) Pages: 66-74
• [Journal Article] Novel SCN3B Mutation Associated With Brugada Syndrome Affects Intracellular Trafficking and Function of Nav1.5 (2012)
  • Author(s): Ishikawa T
  • Journal Title: Circ J Volume: 77 Pages: 959-67
  • Peer Reviewed
• [Journal Article] Phenotype variability in patients carrying KCNJ2 mutations (2012)
  • Author(s): Kimura H
  • Journal Title: Circ Cardiovasc Genet Volume: 5 Pages: 344-53
  • Peer Reviewed
• [Journal Article] Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization (2012)
  • Author(s): Watanabe H
  • Journal Title: Int J Cardiol Volume: 159 Pages: 238-40
  • Peer Reviewed
• [Journal Article] A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents. (2012)
  • Author(s): Hattori T, Makiyama T, Akao M, Ehara E, Ohno S, Iguchi M, Nishio Y, Sasaki K, Itoh H, Yokode M, Kita T, Horie M, Kimura T
  • Journal Title: Cardiovasc Res Volume: 93 Pages: 666-673
  • Peer Reviewed
• [Journal Article] Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population. (2012)
  • Author(s): Miyamoto A, Hayashi H, Yoshino T, Kawaguchi T, Taniguchi A, Itoh H, Sugimoto Y, Itoh M, Makiyama T, Xue JQ, Murakami Y, Horie M
  • Journal Title: Heart Rhythm Volume: 9 Pages: 66-74
  • Peer Reviewed
• [Journal Article] Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization. (2011)
  • 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, Aizaw
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 4(6) Pages: 874-81
• [Journal Article] Identification and functional characterization of KCNQ1 mutations around the exon 7-intron 7 junction affecting the splicing process (2011)
  • Author(s): Tsuji-Wakisaka K, Akao M, Ishii TM, Ashihara T, Makiyama T, Ohno S, Toyoda F, Dochi K, Matsuura H, Horie M.
  • Journal Title: Biochim Biophys Acta Volume: 1812(11) Pages: 1452-9
• [Journal Article] A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome. (2011)
  • Author(s): DoiT,MakiyamaT,MorimotoT,HarunaY,TsujiK,OhnoS,AkaoM,TakahashiY,KimuraT,HorieM
  • Journal Title: Circ Cardiovasc Genet. Volume: 4(3) Pages: 253-60
• [Journal Article] KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation (2011)
  • Author(s): Ohno S, Zankov D, Ding W, MakiyamaT, Doi T, Shizuta S, Itoh H, Nishio Y, Hattori T, Matsuura H, Horie M.
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: 4(3) Pages: 352-61
• [Journal Article] 循環器疾患の発症機序解明における iPS 細胞の可能性 (2011)
  • Author(s): 牧山武
  • Journal Title: 循環器内科 Volume: 70(5) Pages: 530-536
  • NAID: 40019123504
• [Journal Article] A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome. (2011)
  • Author(s): Tsuji-Wakisaka K, Akao M, Ishii TM, Ashihara T, Makiyama T, Ohno S, Toyoda F, Dochi K, Matsuura H, Horie M
  • Journal Title: Circ Cardiovasc Genet Volume: 1812 Pages: 1452-1459
  • Peer Reviewed
• [Journal Article] novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome. (2011)
  • Author(s): Doi T, Makiyama T, Morimoto T, Haruna Y, Tsuji K, Ohno S, Akao M, Takahashi Y, Kimura T, Horie M
  • Journal Title: Circ Cardiovasc Genet Volume: 4 Pages: 253-260
  • Peer Reviewed
• [Journal Article] KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation. (2011)
  • Author(s): Ohno S, Zankov D, Ding W, Makiyama T, Doi T, Shizuta S, Itoh H, Nishio Y, Hattori T, Matsuura H, Horie M
  • Journal Title: Circ Arrhythm Electrophysiol Volume: 4 Pages: 352-361
  • Peer Reviewed
• [Journal Article] 循環器疾患の発症機序解明におけるiPS細胞の可能性 (2011)
  • Author(s): 牧山武
  • Journal Title: 循環器内科 Volume: 70 Pages: 530-536
  • NAID: 40019123504
• [Presentation] Disease Modeling in Human Induced Pluripotent Stem Cells-Catecholaminergic Polymorphic Ventricular Tachycardia- (2013)
  • Author(s): 牧山武
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] O Ca2+ Imaging of Cardiomyocytes Differentiated from Human Induced Pluripotent Stem Cells in Catecholaminergic Polymorphic Ventricular Tachycardia (2013)
  • Author(s): 佐々木 健一
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] One Year Assessment ofIon Channel Gene Expression in Cardiomyocytes derived from Human Induced Pluripotent Stem Cells (2013)
  • Author(s): 佐々木 健一
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Identification of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells using a Cardiac Specific Lentiviral Vector (2013)
  • Author(s): Yimin Wuriyanghai
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Disease Modeling in Human Induced Pluripotent Stem Cells -Catecholaminergic Polymorphic Ventricular Tachycardia (2013)
  • Author(s): 牧山武
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Ca2+ Imaging of Cardiomyocytes Differentiated from Human Induced Pluripotent Stem Cells in Catecholaminergic Polymorphic Ventricular Tachycardia (2013)
  • Author(s): 佐々木健一
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Phenotypic characteristics between SCN5A and LMNA mutation carriers in familial bradyarrhythmic disorders (2012)
  • Author(s): 牧山武
  • Organizer: The 5thAsia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] One-year assessment of the ultrastructural changes of human induced pluripotent stem cell-derived cardiomyocytes (2012)
  • Author(s): 鎌倉 令
  • Organizer: European Society of Cardiology (ESC) Congress
  • Place of Presentation: Munich,Germany
• [Presentation] Genetic Backgrounds in Patients with Early-Onset and Familial Atrial Fibrillation (2012)
  • Author(s): 鎌倉 令
  • Organizer: The 5thAsia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] One Year Assessment ofIon Channel Gene Expression in Cardiomyocytes derived from Human Induced Pluripotent Stem Cells (2012)
  • Author(s): 佐々木 健一
  • Organizer: The 5thAsia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Analysis of Cardiomyocytes Differentiated from Disease-specific Induced Pluripotent Stem Cells from a Patient with Lamin A/C-related Cardiomyopathy . (2012)
  • Author(s): 牧山武
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
• [Presentation] Genetic Analysis of Candidate Gene Mutations in Patients with Short QT Syndrome (2012)
  • Author(s): 服部哲久
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
• [Presentation] Over-expression of heterozygous KCNJ2-M301K channels, identified in a patient with short QT syndrome (2012)
  • Author(s): 服部哲久
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
• [Presentation] ヒト iPS 細胞由来心筋細胞の電子顕微鏡所見 (2012)
  • Author(s): 鎌倉 令
  • Organizer: 第33回心筋生検研究会
  • Place of Presentation: 京都
• [Presentation] Phenotypic characteristics between SCN5A and LMNA mutation carriers in familial bradyarrhythmic disorders (2012)
  • Author(s): 牧山武
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] One-year assessment of the ultrastructural changes of human induced pluripotent stem cell-derived cardiomyocytes (2012)
  • Author(s): 鎌倉令
  • Organizer: European Society of Cardiology (ESC) Congress
  • Place of Presentation: Munich, Germany
• [Presentation] One Year Assessment of Ion Channel Gene Expression in Cardiomyocytes derived from Human Induced Pluripotent Stem Cells (2012)
  • Author(s): 佐々木健一
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Genetic Backgrounds in Patients with Early-Onset and Familial Atrial Fibrillation (2012)
  • Author(s): 鎌倉令
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] nalysis of Cardiomyocytes Differentiated from Disease-specific Induced Pluripotent Stem Cells from a Patient with Lamin A/C-related Cardiomyopathy. (2012)
  • Author(s): 牧山武
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] Genetic Analysis of Candidate Gene Mutations in Patients with Short QT Syndrome. (2012)
  • Author(s): 服部哲久
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] Over-expression of heterozygous KCNJ2-M301K channels, identified in a patient with short QT syndrome (2012)
  • Author(s): 服部哲久
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡）
• [Presentation] Analysis of Cardiomyocytes Differentiated from Disease-specific Induced Pluripotent Stem Cells from a Patient with Lamin A/C-related Cardiomyopathy . (2011)
  • Author(s): 牧山武
  • Organizer: American Heart Association
  • Place of Presentation: Orland, USA
  • Year and Date: 2011-11-16
• [Presentation] Establishment of Disease-specific Induced Pluripotent Stem Cells from a Patient with Lamin A/C-related Cardiomyopathy (2011)
  • Author(s): 牧山武
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Analysis of Cardiomyocytes Differentiated from Disease-specific Induced Pluripotent Stem Cells from a Patient with Lamin A/C-related Cardiomyopathy. (2011)
  • Author(s): 牧山武
  • Organizer: American Heart Association 2011
  • Place of Presentation: Orange County Convention Center(Orland, USA)
• [Presentation] Establishment of Disease-specific Induced Pluripotent Stem Cells from a Patient with Lamin A/C-related Cardiomyopathy. (2011)
  • Author(s): 牧山武
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] ヒトiPS細胞由来心筋細胞の電子顕微鏡所見 (2011)
  • Author(s): 鎌倉令
  • Organizer: 第33 回心筋生検研究会
  • Place of Presentation: 京都大学 百周年時計台記念館 百周年記念ホール（京都）
• [Presentation] Over-expression of heterozygous KCNJ2-M301K channels, identified in a patient with short QT syndrome (2011)
  • Author(s): 服部哲久
  • Organizer: European Society of Cardiology 2011
  • Place of Presentation: Paris Nord Villepinte(Paris, France)