Role of fibrosis and mechanical stretch in the genesis of atrial fibrillation

• Project/Area Number: 24590487
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TANAKA Hideo 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60236619)
• Co-Investigator(Kenkyū-buntansha): ADACHI Tetsuya 湊川短期大学, 教授 (60345014)
• Co-Investigator(Renkei-kenkyūsha): MATSUYAMA Taka-aki 国立循環器病研究センター, 医員 (40349113)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 心房細動 / カルシウム / 線維化 / 心房 / ギャップ結合 / 心筋 / 興奮伝導 / 間質 / 心筋梗塞 / カルシウムオルタナンス

Outline of Final Research Achievements

This experimental study was conducted to test the possibility that regionally non-uniform mechanical stretch of atrial tissue with the adjacent fibrotic tissues contributes to genesis of atrial fibrillation (AF). By using fast fluorescence imaging of excitation patterns of the excised, perfused rat hearts, we found that 1) the culprit lesions of AF involve a significant increase in fibrosis and 2) rapid pacing of the atria exhibited spatiotemporally inhomogeneous calcium dynamics, both of which may lead to inhomogeneous atrial contractions and the resultant derangement of conduction.

Research Products

• [Journal Article] How Does the Ca²⁺-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca²⁺ Dynamics and Cell Structures in Perfused Rat Hearts— (2015)
  • Author(s): Mani H, Tanaka H, Adachi T, Ikegawa M, Dai P, Fujita N, Takamatsu T.
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 48 Issue: 1 Pages: 1-8
  • DOI: 10.1267/ahc.14059
  • NAID: 130004902931
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The involvement of the vasa vasorum in the development of vasculitis in animal model of Kawasaki disease. (2014)
  • Author(s): Hamaoka-Okamoto A, Suzuki C, Yahata T, Ikeda K, Nagi-Miura N, Ohno N, Arai Y, Tanaka H, Takamatsu T, Hamaoka K.
  • Journal Title: Pediat Rheumatol Volume: 12 Issue: 1 Pages: 1-12
  • DOI: 10.1186/1546-0096-12-12
  • Peer Reviewed / Open Access
• [Journal Article] Photoacoustic microscopy using ultrashort pulses with two different pulse durations (2014)
  • Author(s): Yamaoka Y, Harada Y, Sakakura M, Minamikawa T, Nishino S, Maehara S, Hamano S, Tanaka H, Takamatsu T
  • Journal Title: Opt. Express Volume: 22 Issue: 14 Pages: 17063-17072
  • DOI: 10.1364/oe.22.017063
  • Peer Reviewed
• [Journal Article] Combining TGF-β signal inhibition and connexin43 silencing for iPSC induction from mouse cardiomyocytes. (2014)
  • Author(s): Dai P, Harada Y, Miyachi H, Tanaka H, Kitano S, Adachi T, Suzuki T, Hino H, Takamatsu T.
  • Journal Title: Sci Rep Volume: 4 Issue: 1
  • DOI: 10.1038/srep07323
  • Peer Reviewed / Open Access
• [Journal Article] Formation of contraction bands of heart muscle cells by spatially high-regional ablation of beta-dystroglycan via multiphoton excitation-evoked CALI (2014)
  • Author(s): Tanaka H, Adachi T, Yamaoka Y, Takahashi M, Takamatsu T.
  • Journal Title: Cardiovasc Res Volume: 103 Issue: suppl 1 Pages: S88.5-S89
  • DOI: 10.1093/cvr/cvu091.160
  • Peer Reviewed / Open Access
• [Journal Article] Pacing-Induced Non-Uniform Ca²⁺ Dynamics in Rat Atria Revealed by Rapid-Scanning Confocal Microscopy (2014)
  • Author(s): Yan Jiang, Hideo Tanaka, Taka-aki Matsuyama, Yoshihisa Yamaoka, Tetsuro Takamatsu
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 47 Issue: 2 Pages: 59-65
  • DOI: 10.1267/ahc.14014
  • NAID: 130003390850
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed
• [Journal Article] Intrinsic left atrial histoanatomy as the basis for reentrant excitation causing atrial fibrillation/flutter in rats (2013)
  • Author(s): Matsuyama T, Tanaka H, Adachi T, Jiang Y, Ishibashi-Ueda H, Takamatsu T
  • Journal Title: Heart Rhythm Volume: 10 Issue: 9 Pages: 1342-1348
  • DOI: 10.1016/j.hrthm.2013.04.021
  • Peer Reviewed
• [Presentation] 心筋組織・線維芽細胞組織間の不均一なギャップ結合コミュニケーションは不整脈を惹起する (2014)
  • Author(s): 田中秀央、足達哲也、姜艶、髙松哲郎
  • Organizer: 第36回心筋生検研究会
  • Place of Presentation: 名古屋市
  • Year and Date: 2014-11-28
• [Presentation] 心房の構造に起因する不整脈源性基盤 - カルシウム動態の時空的不均一性 - (2014)
  • Author(s): 田中秀央、姜艶、足達哲也、松山高明、山岡禎久、髙松哲郎
  • Organizer: 第55回日本組織細胞化学会学術集会
  • Place of Presentation: 松本市
  • Year and Date: 2014-09-27
• [Presentation] 梗塞心の致死性不整脈発生におけるプルキンエ線維の役割 - カルシウム動態の時空的不均一性 - (2014)
  • Author(s): 松山高明、田中秀央、大平卓、植田初江、髙松哲郎
  • Organizer: 第55回日本組織細胞化学会学術集会
  • Place of Presentation: 松本市
  • Year and Date: 2014-09-27
• [Presentation] 顕微鏡の上手な使い方 (2014)
  • Author(s): 田中秀央
  • Organizer: 第39回組織細胞化学講習会
  • Place of Presentation: 大津市
  • Year and Date: 2014-08-07
  • Invited
• [Presentation] Formation of contraction bands of heart muscle cells by spatially high-regional ablation of beta dystroglycan via multiphoton excitation-evoked CALI (2014)
  • Author(s): Tanaka H, Adachi T, Yamaoka Y, Takahashi M, Takamatsu T.
  • Organizer: Frontiers in Cardiovascular Biology, FCVB 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-07-05
• [Presentation] ラット心房筋の不整脈原性Ca2+動態 (2014)
  • Author(s): 松山高明、田中秀央、足達哲也、姜艶、植田初江、髙松哲郎
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島市
  • Year and Date: 2014-04-26
• [Presentation] 心筋βジストログリカン（βDG）の破綻はカルシウム濃度上昇を伴って収縮帯形成をもたらす (2014)
  • Author(s): 田中秀央、足達哲也、高橋麻矢子、山岡禎久、髙松哲郎
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島市
  • Year and Date: 2014-04-26
• [Presentation] なぜ不整脈は起こるのか - 心筋機能分子の動態の可視化からその起源を探る - (2014)
  • Author(s): 田中秀央
  • Organizer: 第11回東京心臓病理フォーラム
  • Place of Presentation: 東京都
  • Invited
• [Presentation] 心房組織・線維芽細胞組織間の不均一なギャップ結合コミュニケーションは催不整脈性を増強する (2013)
  • Author(s): 田中秀央、足達哲也、姜艶、髙松哲郎
  • Organizer: 第３０回日本心電学会学術集会
  • Place of Presentation: 青森市
• [Presentation] 梗塞境界部を起源とする不整脈の発生基盤 - 心筋・筋線維芽細胞間ギャップ結合の空間的不均一性のｊ関与 - (2013)
  • Author(s): 田中秀央、足達哲也、姜艶、橋本恵美、髙松哲郎
  • Organizer: 第102回日本病理学会秋期特別総会
  • Place of Presentation: 甲府市
• [Presentation] Intrinsic left atrial histoanatomy as the basis for reentrant excitation causing atrial fibrillation/flutter in rats (2013)
  • Author(s): Taka-aki Matsuyama, Hideo Tanaka, Tetsuya Adachi, Yan Jiang, Hatsue Ishibashi- Ueda, Tetsuro Takamatsu
  • Organizer: 37th International Congress of Physiological Sciences (IUPS2013)
  • Place of Presentation: Birmingham, UK
• [Presentation] Generation of reentrant arrhythmias by spatially non-uniform gap-junction connection with myofibroblasts in rat cultured myocyte monolayers (2013)
  • Author(s): Tetsuya Adachi, Yan Jiang, Hideo Tanaka, Emi Hashimoto, Tetsuro Takamatsu
  • Organizer: 37th International Congress of Physiological Sciences (IUPS2013)
  • Place of Presentation: Birmingham, UK
• [Presentation] Arrhythmogenic intracellular calcium waves in the heart imaged by rapid-scanning confocal microscopy (2013)
  • Author(s): Hideo Tanaka
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 内在性心房細動器質の探索 - 健常ラット心の光学的マッピングと組織解析による統合的検討 - (2012)
  • Author(s): 松山高明、田中秀央、足達哲也、姜艶、植田初江、髙松哲郎
  • Organizer: 第29回日本心電学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Intrinsic histological basis for the preferential excitaion of atrial fibrillation/flutter in rat hearts (2012)
  • Author(s): Matsuyama T, Tanaka H, Adachi T, Jiang Y, Ishibasi-Ueda H, Takamatsu T.
  • Organizer: 14th International Congress of Histochemistry and Cytochemistry
  • Place of Presentation: 京都
• [Book] 顕微鏡の上手な使い方 (2014)
  • Author(s): 田中秀央、山岡禎久
  • Total Pages: 8
  • Publisher: 中西印刷株式会社