In vivo left ventricular functional capacity is compromised in cMyBP-C null mice.
Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that binds tightly to myosin and has a potential role for modulating myocardial contraction. We tested the hypothesis that cMyBP-C 1) contributes to the enhanced in vivo contractile state following beta-adrenergic stimulation and 2) is necessary for myocardial adaptation to chronic increases in afterload. In vivo pressure-volume relations demonstrated that left ventricular (LV) systolic and diastolic function were compromised under basal conditions in cMyBP-C(-/-) compared with WT mice. Moreover, whereas beta-adrenergic treatment significantly improved ejection fraction, peak elastance, and the time to peak elastance in WT mice, these functional indexes remained unchanged in cMyBP-C(-/-) mice. Morphological and functional changes were measured through echocardiography in anesthetized mice following 5 wk of aortic banding. Adaptation to pressure overload was diminished in cMyBP-C(-/-) mice as characterized by a lack of an increase in posterior wall thickness, increased LV diameter, deterioration of fractional shortening, and prolonged isovolumic relaxation time. These results suggest that the absence of cMyBP-C significantly diminishes in vivo LV function and markedly attenuates the increase in LV contractility following beta-adrenergic stimulation or adaptation to pressure overload.
Brickson
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Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53711, USA. sbrickson@physiology.wisc.edu
Fitzsimons
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Pereira
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Hacker
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Valdivia
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Moss
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003971:Diastole / Q000187:drug effects / Q000502:physiology*; D004280:Dobutamine / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000502:physiology; D013599:Systole / Q000187:drug effects / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D024723:Ventricular Myosins / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology; D000099163:Myosin Binding Protein C
D000318:Adrenergic beta-Agonists; D002118:Calcium; D002352:Carrier Proteins; D004280:Dobutamine; D024723:Ventricular Myosins; D000099163:Myosin Binding Protein C