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Gene analysis for the inherited bradyarrhythmia and characterization of cardiosphere-derived cells to create biological pacemakers

Research Project

Project/Area Number 22590806
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKanazawa University

Principal Investigator

HAYASHI Kenshi  金沢大学, 大学病院, 助教 (00422642)

Co-Investigator(Kenkyū-buntansha) FUJINO Noboru  金沢大学, 保健学系, 准教授 (40361993)
KURATA Yasutaka  金沢医科大学, 医学部, 准教授 (00267725)
YAMAGISHI Masakazu  金沢大学, 医学系, 教授 (70393238)
Co-Investigator(Renkei-kenkyūsha) HIGASHIDA Haruhiro  金沢大学, 子供のこころ発達研究センター, 教授 (30093066)
SAKAMOTO Yuichiro  金沢大学, 大学病院, 助教 (70467108)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords先天性徐脈 / 遺伝子解析 / 心筋前駆細胞 / 生物学的ペースメーカー / 徐脈性不整脈 / 遺伝子変異 / パッチクランプ / 循環器 / 遺伝子 / 再生医学 / シミュレーション工学 / 生理学
Research Abstract

We evaluated clinical characteristics and performed gene analysis for 58 patients with inherited bradyarrhythmia. Twenty six patients (45%) had family history of bradyarrhythmia and 24 patients (41%) underwent pacemaker implantation. Gene analysis showed mutations were found in 7 patients (12%) who were complicated by QT prolongation, atrial fibrillation, or muscular dystrophy. Cellular electrophysiological study showed functional abnormality in 3 of 4 ion channel gene mutations. We isolated cardiosphere-derived cells from the neonatal mouse heart and confirmed that some cells contracted spontaneously. Patch clamp and RT-PCR showed that at least two types of ionic currents were present in mouse cardiosphere-derived cells including a delayed rectifier K+current and an inward rectifier K+current.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report

Research Products

(46 results)

All 2013 2012 2011 2010 Other

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (18 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Effect of hyperpolarization-activated current If on robustness of sinoatrial node pacemaking: theoretical study on influence of intracellular Na+ concentration2013

    • Author(s)
      Kurata Y
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 304 Pages: 61-7

    • DOI

      10.1152/ajpheart.00777.2012

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel mutation in the transmembrane nonpore region of the KCNH2 gene causes severe clinical manifestations of long QT syndrome2013

    • Author(s)
      Kurata Y
    • Journal Title

      Heart Rhythm.

      Volume: 10 Pages: 61-67

    • DOI

      10.1016/j.hrthm.2012.09.053

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel mutation in the transmembrane nonpore region of the KCNH2 gene causes severe clinical manifestations of long QT syndrome.2013

    • Author(s)
      Liu L
    • Journal Title

      Heart Rhythm.

      Volume: 10 Pages: 61-7

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Systolic Dysfunction in Genotyped Hypertrophic Cardiomyopathy2013

    • Author(s)
      Fhujino N
    • Journal Title

      Clin Cardiol.

      Volume: 36 Pages: 160-5

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transient expression of cellular retinol-binding protein-1 during cardiac repair after myocardial infarction.2012

    • Author(s)
      Yu M
    • Journal Title

      Pathol Int

      Volume: 62 Pages: 246-53

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perfect correspondence of mitral valve perforation using real-time 3-dimensional transesophageal echocardiography.2012

    • Author(s)
      Tada H
    • Journal Title

      J Am Coll Cardiol.

      Volume: 59 Pages: 1914-1914

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Post-prandial remnant lipoprotein metabolism in autosomal recessive hypercholesterolaemia.2012

    • Author(s)
      Tada H
    • Journal Title

      Eur J Clin Invest.

      Volume: 42 Pages: 1094-9

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of visceral adipose tissue and subcutaneous adipose tissue on insulin resistance in middle-aged Japanese.2012

    • Author(s)
      Oka R
    • Journal Title

      Atheroscler Thromb.

      Volume: 19 Pages: 814-22

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress-induced takotsubo cardiomyopathy complicated with wall rupture and thrombus formation.2012

    • Author(s)
      Yoshida S
    • Journal Title

      Int J Cardiol.

      Volume: 161

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of visceral adipose tissue and subcutaneous adipose tissue on insulin resistance in middle-aged Japanese.2012

    • Author(s)
      Oka R
    • Journal Title

      J Atheroscler Thromb.

      Volume: 19 Pages: 814-22

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anomalous origin with myocardial bridging in coronary artery: stealth images in computed tomography.2012

    • Author(s)
      Yamamoto R
    • Journal Title

      J Am Coll Cardiol.

      Volume: 60 Pages: 84-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid changes in plaque composition and morphology after intensive lipid lowering therapy: study with serial coronary2012

    • Author(s)
      Shimojima M
    • Journal Title

      Am J Cardiovasc Dis.

      Volume: 2 Pages: 84-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Altered metabolism of low-density lipoprotein and very-low-density lipoprotein remnant in autosomal recessive hypercholesterolemia : results from stable isotope kinetic study in vivo2012

    • Author(s)
      Tada H, Hayashi K, Yamagishi M
    • Journal Title

      Circ Cardiovasc Genet

      Volume: 5 Pages: 35-41

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of coadministration of rosuvastatin, ezetimibe, and colestimide in heterozygous familial hypercholesterolemia2012

    • Author(s)
      Kawashiri MA, Hayashi K, Yamagishi M
    • Journal Title

      Am J Cardiol

      Volume: 109 Pages: 364-9

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene and protein expression analysis of mesenchymal stem cells derived from rat adipose tissue and bone marrow2011

    • Author(s)
      Nakanishi C, Hayashi K, Yamagishi M
    • Journal Title

      Circ J

      Volume: 75 Pages: 2260-8

    • NAID

      10029340006

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A KCR1 Variant Implicated in Susceptibility to the Long QT Syndrome2011

    • Author(s)
      HayashiK, FujinoN, Yamagishi M
    • Journal Title

      J Mol Cell Cardiol

      Volume: 50 Pages: 50-57

    • DOI

      10.1016/j.yjmcc.2010.10.007

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability2011

    • Author(s)
      Kurata Y
    • Journal Title

      Circulation Research

      Volume: 108 Pages: 458-468

    • DOI

      10.1161/circresaha.110.227835

    • NAID

      130002130408

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel type of familial hypercholesterolemia : double heterozygous mutations in LDL receptor and LDL receptor adaptorprotein 1 gene2011

    • Author(s)
      Tada H, Hayashi K, Yamagishi M
    • Journal Title

      Atherosclerosis

      Volume: 219 Pages: 663-6

    • NAID

      120003628222

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of severe coronary disease associated or not associated with diabetes mellitus on outcome of interventional treatment using stents : results from HERZ (Heart Research Group of Kanazawa) analyses2011

    • Author(s)
      Uchiyama K, Hayashi K, Yamagishi M
    • Journal Title

      J Int Med Res

      Volume: 39 Pages: 549-57

    • NAID

      120006407090

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A KCR1 variant implicated in susceptibility to the long QT syndrome.2011

    • Author(s)
      Hayashi K
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 50 Pages: 50-57

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability.2011

    • Author(s)
      Li P
    • Journal Title

      Circ Res

      Volume: 108 Pages: 456-468

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long QT syndrome with compound mutations is associated with a more severe phenotype: A Japanese multicenter study2010

    • Author(s)
      Itoh H, Hayashi K, Yamagishi M, Horie M
    • Journal Title

      Heart Rhythm

      Volume: 7 Pages: 1411-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trafficking-Competent KCNQ1 Variably Influences the Function of HERG Long QT Alleles2010

    • Author(s)
      Hayashi K, Yamagishi M
    • Journal Title

      Heart Rhythm

      Volume: 7 Pages: 973-80

    • DOI

      10.1016/j.hrthm.2010.03.038

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Trafficking-competent KCNQ1 variably influences the function of HERG long QT alleles.2010

    • Author(s)
      Hayashi K
    • Journal Title

      Heart Rhythm

      Volume: 7 Pages: 973-980

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long QT syndrome with compound mutations is associated with a more severe phenotype : a Japanese multicenter study.2010

    • Author(s)
      Itoh H
    • Journal Title

      Heart Rhythm

      Volume: 7 Pages: 1411-1418

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Long QT Syndrome Mutation Carriers in Japanese School Children and Their Clinical Course2013

    • Author(s)
      林 研至,藤野陽,山岸正和
    • Organizer
      The 77th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      パシフィコ横浜(神奈川県
    • Year and Date
      2013-03-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Functional Characterization of Cardiac Ion Channel Gene Variants in Lone Atrial Fibrillation2012

    • Author(s)
      Kenshi Hayashi, Noboru Fujino, Masakazu Yamagishi
    • Organizer
      American Heart Association SCIENTIFIC SESSIONS 2012
    • Place of Presentation
      Los Angeles Convention Center (USA)
    • Year and Date
      2012-11-07
    • Related Report
      2012 Final Research Report
  • [Presentation] 孤立性心房細動に認められる遺伝子異常とその意義2012

    • Author(s)
      林 研至,藤野陽,倉田康孝,山岸正和
    • Organizer
      he 27th Annual Meeting of the Japanese Heart Rhythm Society
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2012-07-06
    • Related Report
      2012 Final Research Report
  • [Presentation] Prevalence and Outcomes of Young Athletes in Congenital Long QT Syndrome: Results from School Cardiac Screening and Gene Analysis2012

    • Author(s)
      林 研至,藤野陽,山岸正和
    • Organizer
      The 76th Annual Scientific Meeting of the Japanese Circulation Society Symposium 12
    • Place of Presentation
      Fukuoka International Congress Center(福岡)
    • Year and Date
      2012-03-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Cardiac ion channel mutations in acquired long QT syndrome2012

    • Author(s)
      林 研至,藤野陽,山岸正和
    • Organizer
      The 76th Annual Scientific Meeting of the Japanese Circulation Society Asian Joint Case-Conference 8
    • Place of Presentation
      Fukuoka International Congress Center(福岡)
    • Year and Date
      2012-03-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Functional Characterization of Cardiac Ion Channel Gene Variants in Lone Atrial Fibrillation2012

    • Author(s)
      Kenshi Hayashi
    • Organizer
      American Heart Association SCIENTIFIC SESSIONS 2012
    • Place of Presentation
      Los Angeles Convention Center, Los Angeles, CA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Prevalence and Outcomes of Young Athletes in Congenital Long QT Syndrome : Results from School Cardiac Screening and Gene Analysis2012

    • Author(s)
      Kenshi Hayashi
    • Organizer
      The 76th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka International Congress Center, Fukuoka, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cardiac ion channel mutations in acquired long QT syndrome2012

    • Author(s)
      Kenshi Hayashi
    • Organizer
      The 76th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka International Congress Center, Fukuoka, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] Trafficking-Competent KCNQ1 Variably Influences the Function of HERG Long QT Alleles2011

    • Author(s)
      Kenshi Hayashi, Noboru Fujino, Masakazu Yamagishi
    • Organizer
      32nd Annual Scientific Sessions
    • Place of Presentation
      Moscone Center(USA)
    • Year and Date
      2011-05-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of Compound Heterozygosity for Mutations R269W in KCNH2 and P1824A in SCN5A Associated with Long QT Syndrome and Sinus Node Dysfunction2011

    • Author(s)
      Kenshi Hayashi, Noboru Fujino, Yasutaka Kurata, Masakazu Yamagishi
    • Organizer
      ACC.11 60th Annual Scientific Session
    • Place of Presentation
      Morial Convention Center (USA)
    • Year and Date
      2011-04-05
    • Related Report
      2012 Final Research Report
  • [Presentation] Impact of Gene Variants of KCNH2 and SCN5A on Occurrence of Lone Atrial Fibrillation2011

    • Author(s)
      Liu L
    • Organizer
      The 73rd Annual Scientific Meeting of theJapanese Circulation Society
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2011-03-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Trafficking-Competent KCNQ1 Variably Influences the Function of HERG Long QT Alleles2011

    • Author(s)
      Kenshi Hayashi
    • Organizer
      Heart Rhythm 2011, 32nd Annual Scientific Sessions
    • Place of Presentation
      Moscone Center, San Francisco, CA
    • Related Report
      2011 Annual Research Report
  • [Presentation] Genetic analysis for the inherited bradyarrhythmia2010

    • Author(s)
      林 研至,藤野陽,倉田康孝,山岸正和
    • Organizer
      The 25th Annual Meeting of the Japanese Heart Rhythm Society / Symposium
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2010-06-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Genetic analysis for the inherited bradyarrhythmia2010

    • Author(s)
      Hayashi K
    • Organizer
      The 25th Annual Meeting of the Japan Heart Rhythm Society
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2010-06-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝硬変患者で認められるQT延長とその成因に関する検討2010

    • Author(s)
      Sakurai H
    • Organizer
      The 25th Annual Meeting of the Japan Heart Rhythm Society
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2010-06-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Characterization of compound heterozygosity for mutations R269W in KCNH2 and P1824A in SCN5A associated with long QT syndrome and sinus node dysfunction2010

    • Author(s)
      Hayashi K
    • Organizer
      20th World Congress of the ISHR 2010
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2010-05-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] 孤立性心房細動に認められる遺伝子異常とその意義

    • Author(s)
      林 研至
    • Organizer
      The 27th Annual Meeting of the Japanese Heart Rhythm Society
    • Place of Presentation
      パシフィコ横浜, 横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Long QT Syndrome Mutation Carriers in Japanese School Children and Their Clinical Course

    • Author(s)
      Kenshi Hayashi
    • Organizer
      The 77th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      パシフィコ横浜, 横浜
    • Related Report
      2012 Annual Research Report
  • [Book] 肥大型心筋症2010

    • Author(s)
      今野哲雄
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://intmed2.w3.kanazawa-u.ac.jp/index_j.html

    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://intmed2.w3.kanazawa-u.ac.jp/index_j.html

    • Related Report
      2011 Annual Research Report

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Published: 2010-08-22   Modified: 2019-07-29  

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