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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概要
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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.
著者
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TAKAKI Miyako
Department of Physiology II, Nara Medical University
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YAGI Naoto
Research & Utilization Division, Japan Synchrotron Radiation Research Institute
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Kajiya Fumihiko
Department Of Cardiovascular Physiology Okayama University
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Takaki Miyako
Department Of Physiology Ii Nara Medical University
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Toyota Hiroko
Department Of Physiology Kawasaki Medical School
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Kataoka Noriyuki
Department Of Material Science And Technology Kyoto University
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Miura Daiji
Department Of Cardiovascular Medicine Okayama University Graduate School Of Medicine Dentistry And P
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Morita Hiroshi
Department Of Applied Chemistry School Of Engineering Kanagawa University
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Ito Hiroshi
Department Neurosurgery Tokyo Medical College
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Hashimoto Ken
Department Of Cardiology National Hospital Organization Okayama Medical Center
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Okuyama Hiroshi
Department Of Applied Chemistry Science University Of Tokyo
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Ohe Tohru
Department Of Cardiology Okayama University
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Fukushima Kusano
Department Of Cardiovascular Medicine Okayama University
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Miyoshi Toru
Department Of Cardiovascular Medicine Okayama University Graduate School Of Medicine Dentistry And Pharmaceutical Sciences
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Nakamura Kazufumi
Department of Applied Chemistry, Faculty of Science and Technology, Keio University
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Sumita Yoshikawa
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Shimizu Juichiro
Hiroshima International University
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Matsuo Tatsuhito
Research and Utilization Division, Japan Synchrotron Radiation Research Institute, SPring-8
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Fukushima Kusano
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kataoka Noriyuki
Departments of Medical Engineering and Physiology, Kawasaki Medical School
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Yagi Naoto
Research and Utilization Division, Japan Synchrotron Radiation Research Institute, SPring-8
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Kajiya Fumihiko
Departments of Medical Engineering and Physiology, Kawasaki Medical School
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Toyota Hiroko
Departments of Medical Engineering and Physiology, Kawasaki Medical School
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HASHIMOTO KEN
Department o f Surgery, Kurume University School of Medicine
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TOYOTA Hiroko
Department of Medical Engineering and Physiology, Kawasaki Medical School
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