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Normal passive viscoelasticity but abnormal myofibrillar force generation in human hypertrophic cardiomyopathy
- Source :
- Journal of Molecular and Cellular Cardiology
- Publisher :
- Elsevier Ltd.
-
Abstract
- Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, increased ventricular stiffness and impaired diastolic filling. We investigated to what extent myocardial functional defects can be explained by alterations in the passive and active properties of human cardiac myofibrils. Skinned ventricular myocytes were prepared from patients with obstructive HCM (two patients with MYBPC3 mutations, one with a MYH7 mutation, and three with no mutation in either gene) and from four donors. Passive stiffness, viscous properties, and titin isoform expression were similar in HCM myocytes and donor myocytes. Maximal Ca2+-activated force was much lower in HCM myocytes (14 ± 1 kN/m2) than in donor myocytes (23 ± 3 kN/m2; P<br />Research Highlights ► The passive stiffness of skinned HCM cardiac myocytes was similar to that of normal (donor) myocytes. ► Maximum Ca-activated force production was reduced by 40% in HCM vs donor myocytes. ► This loss of force could contribute to systolic dysfunction in HCM hearts. ► Myofibrillar Ca sensitivity was higher in HCM than in donor myocytes. ► The enhanced Ca sensitivity could compensate for the smaller maximum force but would tend to cause diastolic dysfunction. ► These characteristics were common to all HCM patients studied, suggesting the changes were secondary consequence of the underlying genetic variants.
- Subjects :
- Sarcomeres
medicine.medical_specialty
Diastole
Cardiomyopathy
Cross-bridge kinetics
macromolecular substances
Left ventricular hypertrophy
Myofibrils
Stress, Physiological
Isometric Contraction
Internal medicine
medicine
Humans
Myocyte
Myocytes, Cardiac
cardiovascular diseases
Molecular Biology
Viscosity
Chemistry
Hypertrophic cardiomyopathy
Viscoelasticity
Skinned cardiac myocytes
Cardiomyopathy, Hypertrophic
medicine.disease
Ca2+ sensitivity
Elasticity
Biomechanical Phenomena
Kinetics
medicine.anatomical_structure
Highlighted Article
Ventricle
Cardiology
cardiovascular system
Calcium
MYH7
Cardiology and Cardiovascular Medicine
Myofibril
Subjects
Details
- Language :
- English
- ISSN :
- 00222828
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular and Cellular Cardiology
- Accession number :
- edsair.doi.dedup.....1f1c5d353698a9479f038424ee47e119
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2010.06.006