Hypertrophic cardiomyopathy mutations in MYBPC3 dysregulate myosin

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Science Translational Medicine  23 Jan 2019:
Vol. 11, Issue 476, eaat1199
DOI: 10.1126/scitranslmed.aat1199

Manipulating myosin to curb cardiomyopathy

Hypertrophic cardiomyopathy (HCM, thickened heart muscle) is a disease typically caused by mutations in sarcomere genes. Sarcomeres are the functional and structural units in muscle that allow for contraction and relaxation. Toepfer et al. investigated how mutations in cardiac myosin-binding protein C (encoded by MYBPC3) alter cardiac muscle contraction and relaxation. Using mouse models and human muscle fibers, they showed that MYBPC3 mutations increased contractility and decreased relaxation by disrupting myosin conformations. Treating cardiomyocytes with a myosin allosteric inhibitor corrected the relaxation, contraction, and myosin conformation deficits, suggesting that the myosin inhibitor could be therapeutic for HCM.

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