The absence of cMyBP-C significantly diminished in vivo LV function and attenuated the increase in LV contractility following beta-adrenergic stimulation or adaptation to pressure overload in mice.
Does the absence of cMyBP-C impair left ventricular functional capacity and adaptation to stress in mice?
cMyBP-C is essential for normal basal left ventricular function and for myocardial adaptation to beta-adrenergic stimulation and chronic pressure overload.
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 et al. (Thu,) conducted a other in cMyBP-C deficiency. Beta-adrenergic stimulation and aortic banding vs. Wild-type mice was evaluated on Left ventricular systolic and diastolic function. The absence of cMyBP-C significantly diminished in vivo LV function and attenuated the increase in LV contractility following beta-adrenergic stimulation or adaptation to pressure overload in mice.