Mechanisms Triggering Atrial Fibrillation Associated with Mechanical Stretch of Atrium and Metabolic Syndrome

• Project/Area Number: 22590804
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SASANO Tetsuo 東京医科歯科大学, 大学院・保健衛生学研究科, 准教授 (00466898)
• Research Collaborator: FURUKAWA Tetsushi 東京医科歯科大学, 難治疾患研究所, 教授 (80251552)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 心房細動 / マクロファージ / 炎症 / ATP / ギャップジャンクションチャネル / 伸展刺激 / 線維化 / パラクライン作用 / メタボリック症候群

Research Abstract

Although atrial dilatation is well-known risk for atrial fibrillation, the mechanism linking them remains unclear. We aimed to elucidate the mechanism that mechanical stretch induced atrial inflammation, especially focusing the infiltration of macrophage. The stretched atrial myocytes released ATP in extracellular space, which evoked migration of macrophage. The gap junction family channel including pannexin-2 contributed this mechanism. Murine model of atrial stretch showed infiltration of macrophage, followed by inflammation, fibrosis, and atrial tachycardia. A gap junction channel blocker inhibited these changes. This mechanism may play pivotal role for atrial fibrillation under conditions with atrial dilatation.

Research Products

• [Journal Article] Gene therapy for cardiac arrhythmias (2013)
  • Author(s): Sasano T, Takahashi K, Sugiyama K
  • Journal Title: Acta Cardiologica Sinica Volume: 29 Pages: 226-234
• [Journal Article] NOS1AP, an emergent new genetic marker for QT prolongation and sudden cardiac death (2013)
  • Author(s): Chang KC, Sasano T, Huang S
  • Journal Title: Acta Cardiologica Sinica Volume: 29 Pages: 217-225
• [Journal Article] Distribution of the origin of adenosine triphosphatesensitive atrial tachycardias with the earliest activation recorded in the his bundle catheter - are they limited to the immediate vicinity of the his bundle? (2013)
  • Author(s): Nakamura T, Hachiya H, Tanaka Y,Yagishita A, Sugiyama K, Suzuki M, Kawabata M, Sasano T, Hirao K, Isobe M
  • Journal Title: Circ. J Volume: 77 Pages: 626-631
  • URL: https://www.jstage.jst.go.jp/article/circj/77/3/77_CJ-12-1025/_article
• [Journal Article] Distribution of the origin of adenosine triphosphatesensitive atrial tachycardias with the earliest activation recorded in the his bundle catheter - are they limited to the immediate vicinity of the his bundle? -. (2013)
  • Author(s): Nakamura T
  • Journal Title: Circ J Volume: 77 Pages: 626-31
  • Peer Reviewed
• [Journal Article] Gene therapy for cardiac arrhythmias. (2013)
  • Author(s): Sasano T
  • Journal Title: Acta Cardiol Sinica Volume: 29
  • Peer Reviewed
• [Journal Article] NOS1AP, an emergent new genetic marker for QT prolongation and sudden cardiac death. (2013)
  • Author(s): Chang KC
  • Journal Title: Acta Cardiol Sinica Volume: 29
  • Peer Reviewed
• [Journal Article] Stretch of atrial myocytes stimulates recruitment of macrophages via ATP released trhough gap-junction channels (2012)
  • Author(s): Oishi S, Sasano T, Tateishi, Y, Tamura N, Isobe M, Furukawa T
  • Journal Title: J Pharmacol Sci Volume: 120 Pages: 296-304
  • URL: https://www.jstage.jst.go.jp/article/jphs/120/4/120_12202FP/_article
• [Journal Article] Three-dimensional regional strain analysis in porcine myocardial infarction: A 3T magnetic resonance tagging study (2012)
  • Author(s): Soleimanifard S, Abd-Elmoniem K, Sasano T, Agarwal H, Abraham MR, Abraham T, Prince J
  • Journal Title: J Cardiovasc Magn Reson Volume: 14 Issue: 1 Pages: 85-85
  • DOI: 10.1186/1532-429x-14-85
  • Peer Reviewed
• [Journal Article] Connexin43 gene transfer reduces ventricular tachycarfdia susceptibility after myocardial infarction (2012)
  • Author(s): Greener ID, Sasano T, Wan X, Igarashi T, Strom M, Rosenbaum DS, Donahue JK
  • Journal Title: J Am Coll Cardiol Volume: 60 Issue: 12 Pages: 1103-1110
  • DOI: 10.1016/j.jacc.2012.04.042
  • Peer Reviewed
• [Journal Article] Coexistent idiopathic left ventricular tachycardia and atrial fibrillation induced by maintained va conduction during ventricular tachycardia (2012)
  • Author(s): Yagishita A, Hachiya H, Nakamura T, Sugiyama K, Tanaka Y, Sasano T, Kawabata M, Isobe M, Hirao K
  • Journal Title: Pacing Clin. Electrophysiol Volume: 35 Issue: 12
  • DOI: 10.1111/j.1540-8159.2012.03405.x
  • Peer Reviewed
• [Journal Article] Assessment of distribution and evolution of mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance (2012)
  • Author(s): Abd-Elmoniem K, Santaularia Tomas M, Sasano T, Soleimanifard S, Vonken E-J, Youssef A, Agarwal H, Dimaano V, Calkins H, Stuber M, Prince J, Abraham T, Abraham M
  • Journal Title: J Cardiovasc Magn Reson Volume: 14 Issue: 1 Pages: 1-1
  • DOI: 10.1186/1532-429x-14-1
• [Journal Article] Stretch of atrial myocytes stimulates recruitment of macrophages via ATP released trhough gap-junction channels. (2012)
  • Author(s): Oishi S
  • Journal Title: J Pharmacol Sci Volume: 120 Pages: 296-304
  • Peer Reviewed
• [Journal Article] Role of transient receptor potential vanilloid2 in LPS-induced cytokine production in macrophages (2010)
  • Author(s): K. Yamashiro, T. Sasano, K. Tojo, I.Namekata, J. Kurokawa, N. Sawada, T. Suganami, Y. Kamei, H. Tanaka, N. Tajima, K. Utsunomiya, Y. Ogawa, T. Furukawa
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 398 Issue: 2 Pages: 284-289
  • DOI: 10.1016/j.bbrc.2010.06.082
• [Journal Article] Role of transient receptor potential vanilloid 2 in LPS-induced cytokine production in macrophages. (2010)
  • Author(s): Yamashiro K, Sasano T, et al.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 398 Pages: 284-9
  • Peer Reviewed
• [Presentation] Noninvasive Assessment of Local Excitation in Pulmonary Vein and Left Atrium by Novel High-Sensitive Magnetocardiography (2012)
  • Author(s): Sasano T, Terui M, Oya M, Sugiyama K, Maeda S, Tanaka Y, Kawabata M, Yokoyama Y, Hirao K, Matsuura M
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: Taipei
  • Year and Date: 2012-10-04
• [Presentation] Noninvasive Detection of Pulmonary Venous Excitation by Novel High-Sensitive Vector Magnetocardiography (2012)
  • Author(s): Sasano T, Terui M, Nakamura T, Sugiyama K, Yagishita A, Tanaka Y, Kawabata M, Hachiya H, Kawara T, HiraoK
  • Organizer: Heart Rhythm Society meeting
  • Place of Presentation: Boson, USA
  • Year and Date: 2012-05-09
• [Presentation] Scn1a Mutant Knock-in Mouse Revealed Sudden Unexpected Death in Epilepsy (SUDEP) in Dravet Syndrome as Cardiac Arrhythmia Origin (2012)
  • Author(s): Sasano T, et al
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-18
• [Presentation] Genetic Deletion of Nos1ap Enhanced Cardiac Impairment and Death in Oxidative Stress Induced by Doxorubicin (2012)
  • Author(s): Sasano T, et al
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-18
• [Presentation] Immune Cell Recruitment Initiates Atrial Inflammation in Atrial Dilatation and Diabetes via Different Time-course and Mechanism (2012)
  • Author(s): Sasano T, et al
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-16
• [Presentation] Noninvasive Detection of Pulmonary Vein Activity by Novel High-Sensitive Vector Magnetocardiography (2012)
  • Author(s): Sasano T, et al
  • Organizer: 第76回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-16
• [Presentation] NOS1AP Deletion Enhanced Susceptibility to Ventricular Tachyarrhythmias and Cardiac Death in Pressure Overload (2011)
  • Author(s): Sasano T, et al
  • Organizer: American Heart Association
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2011-11-15
• [Presentation] Oxidative Stress Enhances Arrhythmogenicity and Impairment of Cardiac Function in Nos1ap Deleted Mice (2011)
  • Author(s): Sasano T, et al
  • Organizer: 14th Tokyo-Taipei-Seoul Arrhythmia Conference
  • Place of Presentation: Busan, South Korea
  • Year and Date: 2011-10-29
• [Presentation] Genetic Deletion of NOS1AP Induces Ventricular Tachycardia and Sudden Cardiac Death in Pressure Overloaded Condition (2011)
  • Author(s): Sasano T, Matsubara S, Furukawa T, Hirao K, Isobe M
  • Organizer: 2011 Venice Arrhythmia conference
  • Place of Presentation: Venice, Italy
  • Year and Date: 2011-10-10
• [Presentation] Genetic Deletion of NOS1AP Induces Ventricular Tachycardia and Sudden Cardiac Death in Pressure Overloaded Condition (2011)
  • Author(s): Sasano T, et al
  • Organizer: Venice Arrhythmia conference
  • Place of Presentation: Venice, Italy
  • Year and Date: 2011-10-10
• [Presentation] Hyperthermia-induced Ventricular Tachycardia and Sudden Death in Mouse Model of Dravet Syndrome (2011)
  • Author(s): Sasano T, et al
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: 福岡
  • Year and Date: 2011-09-22
• [Presentation] Genetic NOS1AP Deletion Enhances Ventricular Tachycardia and Cardiac Death in Pressure Overload (2011)
  • Author(s): Sasano T, et al
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: 福岡
  • Year and Date: 2011-09-22
• [Presentation] Extracellular ATP Evokes Infiltration of Macrophage in Stretched Atrium (2011)
  • Author(s): Sasano T, et al
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: 福岡
  • Year and Date: 2011-09-21
• [Presentation] Genetic destruction of transcription factor in His-Purkinje system mimicked J wave syndrome in mouse (2011)
  • Author(s): Koizumi A, Sasano T, et al
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: 福岡
  • Year and Date: 2011-09-20
• [Presentation] NOS1AP Destruction Enhanced Susceptibility to Oxidative Stress in Doxorubicin-induced Cardiomyopathy (2011)
  • Author(s): Tsuchiya J, Sasano T, et al
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: 福岡
  • Year and Date: 2011-09-20
• [Presentation] NOS1AP Deletion Enhanced Susceptibility to Ventricular Tachyarrhythmias and Cardiac Death in Pressure Overload (2011)
  • Author(s): Sasano T, Hirao K, Isobe M, Okamura T, Kato N, Furukawa T
  • Organizer: American Heart Association
  • Place of Presentation: Orlando, USA
• [Presentation] Oxidative Stress Enhances Arrhythmogenicity and Impairment of Cardiac Function in Nos1ap Deleted Mice (2011)
  • Author(s): Sasano T, Tsuchiya J, Hirao K, Okamura T, Kato N, Isobe M, Furukawa T
  • Organizer: 14th Tokyo-Taipei-Seoul ArrhythmiaConference
  • Place of Presentation: Busan, South Korea
• [Presentation] Extracellular ATP EvokesInfiltration of Macrophage in Stretched Atrium (2011)
  • Author(s): Sasano T, Oishi S, Tamura N, Isobe M, Furukawa T
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: Fukuoka
• [Presentation] Genetic destruction of transcription factor in His-Purkinje systemmimicked J wave syndrome in mouse (2011)
  • Author(s): Koizumi A, Sasano T, Kimura W, Miura N, Furukawa T
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: Fukuoka
• [Presentation] Genetic NOS1AP Deletion EnhancesVentricular Tachycardia and Cardiac Death in Pressure Overload (2011)
  • Author(s): Sasano T, Matsubara S, Hirao K, Isobe M, Okamura T, Kato N, Furukawa T
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: Fukuoka
• [Presentation] Hyperthermia-induced Ventricular Tachycardia and Sudden Death in Mouse Model of Dravet Syndrome (2011)
  • Author(s): Sasano T, Horigome Y, Takahashi Y, Ogiwara I, Furukawa T
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: Fukuoka
• [Presentation] 心房伸展における細胞外ATPのオートクライン作用を介した炎症メカニズム (2010)
  • Author(s): 笹野哲郎
  • Organizer: 第27回日本心電学会学術集会
  • Place of Presentation: いいちこ文化ホール(大分)
  • Year and Date: 2010-10-09
• [Presentation] Risk and mechanism for sudden cardiac death in NOSIAP knockout mice. (2010)
  • Author(s): 松原清二
  • Organizer: 第14回日本心不全学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2010-10-07
• [Presentation] Autocrine/Paracrine Mechanisms for Macrophage Migration Evoked by Mechanical Stretch of Atrial Myocytes. (2010)
  • Author(s): 笹野哲郎
  • Organizer: 第13回Tokyo-Taipei-Seoul Arrhythmia Conference
  • Place of Presentation: 福岡山王病院(福岡)
  • Year and Date: 2010-10-02
• [Presentation] Nos1APノックアウトマウスにおけるQT間隔及び催不整脈性の検討 (2010)
  • Author(s): 松原清二
  • Organizer: 第25回日本不整脈学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2010-06-11
• [Presentation] Autocrine/Paracrine Mechanisms for Macrophage Migration Evoked by Mechanical Stretch of Atrial Myocytes (2010)
  • Author(s): Sasano T, Oishi S, Furukawa T
  • Organizer: 13th Tokyo-Taipei-Seoul ArrhythmiaConference
  • Place of Presentation: Fukuoka
• [Presentation] Noninvasive Detection of Pulmonary Venous Excitation by Novel High-Sensitive Vector Magnetocardiography.
  • Author(s): Sasano T
  • Organizer: Heart Rhythm Society meeting
  • Place of Presentation: Boston, USA
• [Presentation] Noninvasive Assessment of Local Excitation in Pulmonary Vein and Left Atrium by Novel High-Sensitive Magnetocardiography.
  • Author(s): Sasano T
  • Organizer: Asia-Pacific Heart Rhythm Society meeting
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Electrocardiographic Features Predicting Positive Late Gadolinium Enhancement in Cardiac Magnetic Resonance Imaging.
  • Author(s): Sasano T
  • Organizer: Heart Rhythm Society meeting
  • Place of Presentation: Denver, USA
• [Presentation] 高感度ベクトル心磁計を用いた肺静脈興奮の非侵襲的評価.
  • Author(s): 笹野 哲郎
  • Organizer: 第27回日本不整脈学会
  • Place of Presentation: 横浜
• [Presentation] マウス圧負荷モデルにおける心房炎症と線維化の経時的変化
  • Author(s): 笹野 哲郎
  • Organizer: 第27回日本不整脈学会
  • Place of Presentation: 横浜
• [Presentation] Electrocardiographic Abnormalities Associated with Late Gadolinium Enhancement in Cardiac Magnetic Resonance.
  • Author(s): 笹野 哲郎
  • Organizer: 第77回日本循環器学会
  • Place of Presentation: 横浜
• [Book] Molecular Mechanisms of Cardiac Remodeling. (2013)
  • Author(s): Sasano T
  • Publisher: Springer
• [Book] Molecular Mechanisms of Cardiac Remodeling. Jugdutt BI, Dhalla NS (Eds): Springer, New York, in press (2012)
  • Author(s): Sasano T
  • Publisher: Kurokawa J Remodeling of potassium channels in cardiac hypertrophy In
• [Remarks] 東京医科歯科大学大学院保健衛生学研究科生命機能情報解析学ホームページ
  • URL: http://www.tmd.ac.jp/gradh/bi/index.html
• [Remarks] 東京医科歯科大学難治疾患研究所生体情報薬理学ホームページ
  • URL: http://www.tmd.ac.jp/mri/cph/index.html
• [Remarks] 東京医科歯科大学難治疾患研究所生体情報薬理学ホームページ
  • URL: http://www.tmd.ac.jp/mri/cph/index.html