Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 741-748 |
| Number of pages | 8 |
| Journal | Circulation Journal |
| Volume | 77 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2013 |
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Keywords
- Diastolic dysfunction
- Heart failure
- Myocytes
- Stiffness
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
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. / Yoshikawa, Wakako Sumita; Nakamura, Kazufumi; Miura, Daiji; Shimizu, Juichiro; Hashimoto, Ken; Kataoka, Noriyuki; Toyota, Hiroko; Okuyama, Hiroshi; Miyoshi, Toru; Morita, Hiroshi; Kusano, Kengo Fukushima; Matsuo, Tatsuhito; Takaki, Miyako; Kajiya, Fumihiko; Yagi, Naoto; Ohe, Tohru; Itoh, Hiroshi.
In: Circulation Journal, Vol. 77, No. 3, 2013, p. 741-748.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Yoshikawa, Wakako Sumita
AU - Nakamura, Kazufumi
AU - Miura, Daiji
AU - Shimizu, Juichiro
AU - Hashimoto, Ken
AU - Kataoka, Noriyuki
AU - Toyota, Hiroko
AU - Okuyama, Hiroshi
AU - Miyoshi, Toru
AU - Morita, Hiroshi
AU - Kusano, Kengo Fukushima
AU - Matsuo, Tatsuhito
AU - Takaki, Miyako
AU - Kajiya, Fumihiko
AU - Yagi, Naoto
AU - Ohe, Tohru
AU - Itoh, Hiroshi
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Diastolic dysfunction
KW - Heart failure
KW - Myocytes
KW - Stiffness
UR - http://www.scopus.com/inward/record.url?scp=84874425263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874425263&partnerID=8YFLogxK
U2 - 10.1253/circj.CJ-12-0779
DO - 10.1253/circj.CJ-12-0779
M3 - Article
VL - 77
SP - 741
EP - 748
JO - Circulation Journal
JF - Circulation Journal
SN - 1346-9843
IS - 3
ER -