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.

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. 

• Authors: Wakako Sumita Yoshikawa, Kazufumi Nakamura, Daiji Miura, Juichiro Shimizu, Ken Hashimoto, Noriyuki Kataoka, Hiroko Toyota, Hiroshi Okuyama, Toru Miyoshi, Hiroshi Morita, Kengo Fukushima Kusano, Tatsuhito Matsuo, Miyako Takaki, Fumihiko Kajiya, Naoto Yagi, Tohru Ohe, Hiroshi Ito
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 77 Issue 3 Pg. 741-8 ( 2013) ISSN: 1347-4820 [Electronic] Japan
• PMID: 23220799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Adrenergic beta-Agonists
• Enzyme Inhibitors
• Heterocyclic Compounds, 4 or More Rings
• diacetylmonoxime
• blebbistatin
• Myosins
• Diacetyl
• Isoproterenol

Topics

• Actins (metabolism)
• Adrenergic beta-Agonists (adverse effects, pharmacology)
• Animals
• Cardiomegaly (chemically induced, pathology, physiopathology)
• Cells, Cultured
• Diacetyl (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Elasticity (physiology)
• Enzyme Inhibitors (pharmacology)
• Heterocyclic Compounds, 4 or More Rings (pharmacology)
• Hypertrophy, Left Ventricular (chemically induced, pathology, physiopathology)
• Isoproterenol (adverse effects, pharmacology)
• Male
• Microscopy, Atomic Force
• Myocytes, Cardiac (diagnostic imaging, pathology, physiology)
• Myosins (metabolism)
• Organ Size (drug effects)
• Papillary Muscles (diagnostic imaging, drug effects, pathology)
• Radiography
• Rats
• Rats, Wistar
• Ultrasonography