title: Cardiac myosin binding protein C insufficiency leads to early onset of mechanical dysfunction.
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.
  
  
  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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Candida L
authors.initials: CL
authors.lastname: Desjardins
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Coulton
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hoit
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Julian E
authors.initials: JE
authors.lastname: Stelzer
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D009200:Myocardial Contraction; D016277:Ventricular Function, Left; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C