Format

Send to

Choose Destination
Circ Cardiovasc Imaging. 2012 Jan;5(1):127-36. doi: 10.1161/CIRCIMAGING.111.965772. Epub 2011 Dec 7.

Cardiac myosin binding protein C insufficiency leads to early onset of mechanical dysfunction.

Author information

1
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.

Abstract

BACKGROUND:

Decreased expression of cardiac myosin binding protein C (cMyBPC) as a result of genetic mutations may contribute to the development of hypertrophic cardiomyopathy (HCM); however, the mechanisms that link cMyBPC expression and HCM development, especially contractile dysfunction, remain unclear.

METHODS AND RESULTS:

We evaluated cardiac mechanical function in vitro and in vivo in young mice (8-10 weeks of age) carrying no functional cMyBPC alleles (cMyBPC(-/-)) or 1 functional cMyBPC allele (cMyBPC(±)). Skinned myocardium isolated from cMyBPC(-/-) hearts displayed significant accelerations in stretch activation cross-bridge kinetics. Cardiac MRI studies revealed severely depressed in vivo left ventricular (LV) magnitude and rates of LV wall strain and torsion compared with wild-type (WT) mice. Heterozygous cMyBPC(±) hearts expressed 23±5% less cMyBPC than WT hearts but did not display overt hypertrophy. Skinned myocardium isolated from cMyBPC(±) hearts displayed small accelerations in the rate of stretch induced cross-bridge recruitment. MRI measurements revealed reductions in LV torsion and circumferential strain, as well reduced circumferential strain rates in early systole and diastole.

CONCLUSIONS:

Modest decreases in cMyBPC expression in the mouse heart result in early-onset subtle changes in cross-bridge kinetics and in vivo LV mechanical function, which could contribute to the development of HCM later in life.

PMID:
22157650
PMCID:
PMC3328136
DOI:
10.1161/CIRCIMAGING.111.965772
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center