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

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Author(s)

    • YOSHIKAWA SUMITA 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
    • HASHIMOTO Ken
    • Department of Medical Engineering and Physiology, Kawasaki Medical School
    • KATAOKA Noriyuki
    • Department of Medical Engineering and Physiology, Kawasaki Medical School
    • TOYOTA Hiroko
    • Department of Medical Engineering and Physiology, Kawasaki Medical School
    • OKUYAMA Hiroshi
    • Department 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
    • KUSANO FUKUSHIMA 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
    • KAJIYA Fumihiko
    • Department of Medical Engineering and Physiology, Kawasaki Medical School
    • YAGI Naoto
    • Research and Utilization Division, Japan Synchrotron Radiation Research Institute
    • 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

Abstract

<b><i>Background:</i></b> 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. <b><i>Methods and Results:</i></b> 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<sub>(1,0)</sub>/I<sub>(1,1)</sub>) at diastole was not different before and after treatment with BDM, which induces complete relaxation, in control hearts, but that I<sub>(1,0)</sub>/I<sub>(1,1)</sub> was significantly increased after BDM treatment in the ISO group, indicating residual cross-bridge formation in hypertrophied hearts. <b><i>Conclusions:</i></b> 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.  (<i>Circ J</i> 2013; <b>77</b>: 741–748)<br>

Journal

  • Circulation Journal

    Circulation Journal 77(3), 741-748, 2013-02-25

    The Japanese Circulation Society

References:  44

Codes

  • NII Article ID (NAID)
    10031138966
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13469843
  • Data Source
    CJP  CJPref  J-STAGE 
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