| First Author | Desjardins CL | Year | 2012 |
| Journal | Circ Cardiovasc Imaging | Volume | 5 |
| Issue | 1 | Pages | 127-36 |
| PubMed ID | 22157650 | Mgi Jnum | J:308089 |
| Mgi Id | MGI:6725927 | Doi | 10.1161/CIRCIMAGING.111.965772 |
| Citation | Desjardins CL, et al. (2012) Cardiac myosin binding protein C insufficiency leads to early onset of mechanical dysfunction. Circ Cardiovasc Imaging 5(1):127-36 |
| abstractText | 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. |
