Heart failure & cardiomyopathies
Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy
An erratum to this article was published (Circulation, 10 Mar 2020 ↗)
Authors' conclusion
Myosin conformations establish work-energy equipoise that is essential for life-long cellular homeostasis and heart function. Destabilization of myosin energy-conserving states promotes contractile abnormalities, morphological and metabolic remodeling, and adverse clinical outcomes in patients with HCM.
Study context
- Population
- Healthy rodent and human hearts, at baseline, in hibernation or with pathogenic hypertrophic cardiomyopathy (HCM) variants; patients with HCM carrying myosin variants of unknown significance
Main finding
As reported in the abstract
- Hibernation increased the proportion of myosins in the SRX conformation
- Pathogenic variants destabilized SRX and increased the DRX proportion, enhancing cardiomyocyte contractility but impairing relaxation and evoking hypertrophic remodeling with increased energetic stress
- Variants of unknown significance that destabilized myosin conformations were associated with higher rates of HF and arrhythmias in patients with HCM
Original publication
Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy. Circulation. Published 27 January 2020. doi:10.
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