Triggered Firing and Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Induced by Overexpression of TGF-β1

• Choi Eue-Keun

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

• Chang Po-Cheng

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

• Lee Young-Soo

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

• Lin Shien-Fong

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

• Zhu Wuqiang

  Department of Medicine, Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine

• Maruyama Mitsunori

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

• Fishbein Michael C.

  Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine

• Chen Zhenhui

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

• Rubart-von der Lohe Michael

  Department of Medicine, Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine

• Field Loren J.

  Department of Medicine, Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine

• Chen Peng-Sheng

  Krannert Institute of Cardiology and the Division of Cardiology, Indiana University School of Medicine Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine

抄録

Background: Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Ca_i) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1). Methods and Results: MHC-TGFcys³³ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1. We studied membrane potential and Ca_i transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Ca_i transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca²⁺-ATPase 2a. Conclusions: Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Ca_i transient, EAD and triggered activity. Inhibition of Ca²⁺ release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-β1 Tx atria. (Circ J 2012; 76: 1354-1362)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 76 (6), 1354-1362, 2012

  一般社団法人 日本循環器学会

キーワード

• Arrhythmia
• Atrial fibrillation
• Ca²⁺ triggers
• Optical mapping
• Transgenic mice models

詳細情報

• CRID: 1390001205104133632
• NII論文ID: 10030316001
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-11-1301
• COI: 1:CAS:528:DC%2BC38Xpsl2ktb0%3D
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 22447020
• Web Site: https://www.jstage.jst.go.jp/article/circj/76/6/76_CJ-11-1301/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013173558
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
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