Cardiomyocyte Apoptosis Is Associated with Contractile Dysfunction in Stem Cell Model of MYH7 E848G Hypertrophic Cardiomyopathy.

ABSTRACT: Missense mutations in myosin heavy chain 7 (MYH7) are a common cause of hypertrophic cardiomyopathy (HCM), but the molecular mechanisms underlying MYH7-based HCM remain unclear. In this work, we generated cardiomyocytes derived from isogenic human induced pluripotent stem cells to model the heterozygous pathogenic MYH7 missense variant, E848G, which is associated with left ventricular hypertrophy and adult-onset systolic dysfunction. MYH7^E848G/+ increased cardiomyocyte size and reduced the maximum twitch forces of engineered heart tissue, consistent with the systolic dysfunction in MYH7^E848G/+ HCM patients. Interestingly, MYH7^E848G/+ cardiomyocytes more frequently underwent apoptosis that was associated with increas

SUBMITTER: Loiben AM 

PROVIDER: S-EPMC10003263 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature