Key result
Thick filament HCM mutations nearly double microtissue twitch force and prolong relaxation kinetics.
Population
Human induced pluripotent stem cell-derived cardiomyocytes engineered with four HCM mutations using…
Comparison
Thick filament sarcomere mutations vs Isogenic wild-type control iPSc-derived…
Design
Preclinical
Authors
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Should not yet change HCM management; leaves open whether p53 or contractility-targeted therapies benefit patients.
Absolute Event Rate: 40.9% vs 21.7%
Thick filament HCM mutations cause hypercontractility and p53 activation due to oxidative stress, suggesting p53 as a potential therapeutic target.
Cohn et al. (2018) studied Hypertrophic cardiomyopathy (HCM). Thick filament sarcomere mutations (MYH7 and MYBPC3) vs. Isogenic controls was evaluated on Twitch force in 3-dimensional cardiac microtissue assays. Thick filament HCM mutations resulted in hypercontractility, generating 40.9 µN twitch force compared to 21.7 µN in isogenic controls, and prolonged relaxation kinetics.
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