Increased Passive Stiffness of Cardiomyocytes in the Transverse Direction and Residual Actin and Myosin Cross-Bridge Formation in Hypertrophied Rat Hearts Induced by Chronic β-Adrenergic Stimulation

• Sumita Yoshikawa Wakako

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Nakamura Kazufumi

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Miura Daiji

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Shimizu Juichiro

  Hiroshima International University

• Hashimoto Ken

  Departments of Medical Engineering and Physiology, Kawasaki Medical School

• Kataoka Noriyuki

  Departments of Medical Engineering and Physiology, Kawasaki Medical School

• Toyota Hiroko

  Departments of Medical Engineering and Physiology, Kawasaki Medical School

• Okuyama Hiroshi

  Departments of Medical Engineering and Physiology, Kawasaki Medical School

• Miyoshi Toru

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Morita Hiroshi

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Fukushima Kusano Kengo

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Matsuo Tatsuhito

  Research and Utilization Division, Japan Synchrotron Radiation Research Institute, SPring-8

• Takaki Miyako

  Department of Physiology II, Nara Medical University

• Kajiya Fumihiko

  Departments of Medical Engineering and Physiology, Kawasaki Medical School

• Yagi Naoto

  Research and Utilization Division, Japan Synchrotron Radiation Research Institute, SPring-8

• Ohe Tohru

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

• Ito Hiroshi

  Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

抄録

Background: Left ventricular (LV) hypertrophy is often present in patients with diastolic heart failure. However, stiffness of hypertrophied cardiomyocytes in the transverse direction has not been fully elucidated. The aim of this study was to assess passive cardiomyocyte stiffness of hypertrophied hearts in the transverse direction and the influence of actin-myosin cross-bridge formation on the stiffness. Methods and Results: Wistar rats received a vehicle (control) or isoproterenol (ISO) subcutaneously. After 7 days, compared with the controls, ISO administration had significantly increased heart weight and LV wall thickness and had decreased peak early annular relaxation velocity (e’) assessed by echocardiography. Elastic modulus of living cardiomyocytes in the transverse direction assessed by an atomic force microscope was significantly higher in the ISO group than in controls. We added butanedione monoxime (BDM), an inhibitor of actin-myosin interaction, and blebbistatin, a specific myosin II inhibitor, to the medium. BDM and blebbistatin significantly reduced the elastic modulus of cardiomyocytes in the ISO group. X-ray diffraction analysis showed that the reflection intensity ratio (I_(1,0)/I_(1,1)) at diastole was not different before and after treatment with BDM, which induces complete relaxation, in control hearts, but that I_(1,0)/I_(1,1) was significantly increased after BDM treatment in the ISO group, indicating residual cross-bridge formation in hypertrophied hearts. Conclusions: Passive cardiomyocyte stiffness in the transverse direction is increased in hearts with ISO-induced hypertrophy and this is caused by residual actin-myosin cross-bridge formation.  (Circ J 2013; 77: 741–748)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 77 (3), 741-748, 2013

  一般社団法人 日本循環器学会

キーワード

• Diastolic dysfunction
• Heart failure
• Myocytes
• Stiffness

詳細情報

• CRID: 1390282680082297344
• NII論文ID: 10031138966
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-12-0779
• COI: 1:STN:280:DC%2BC3s7pslGisQ%3D%3D
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 23220799
• Web Site: https://www.jstage.jst.go.jp/article/circj/77/3/77_CJ-12-0779/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014010305
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可