Desensitization of myofilaments to Ca2+ as a therapeutic target for hypertrophic cardiomyopathy with mutations in thin filament proteins.

ABSTRACT:

Background

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder caused mainly by mutations in sarcomeric proteins and is characterized by maladaptive myocardial hypertrophy, diastolic heart failure, increased myofilament Ca(2+) sensitivity, and high susceptibility to sudden death. We tested the following hypothesis: correction of the increased myofilament sensitivity can delay or prevent the development of the HCM phenotype.

Methods and results

We used an HCM mouse model with an E180G mutation in α-tropomyosin (Tm180) that demonstrates increased myofilament Ca(2+) sensitivity, severe hypertrophy, and diastolic dysfunction. To test our hypothesis, we reduced myofilament Ca(2+) sensitivity in Tm180 mice by generating a double transgenic mouse line. We crossed Tm180 m

SUBMITTER: Alves ML 

PROVIDER: S-EPMC4061696 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature