Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations.

ABSTRACT:

Rationale

High-myofilament Ca(2+) sensitivity has been proposed as a trigger of disease pathogenesis in familial hypertrophic cardiomyopathy (HCM) on the basis of in vitro and transgenic mice studies. However, myofilament Ca(2+) sensitivity depends on protein phosphorylation and muscle length, and at present, data in humans are scarce.

Objective

To investigate whether high myofilament Ca(2+) sensitivity and perturbed length-dependent activation are characteristics for human HCM with mutations in thick and thin filament proteins.

Methods and results

Cardiac samples from patients with HCM harboring mutations in genes encoding thick (MYH7, MYBPC3) and thin (TNNT2, TNNI3, TPM1) filament proteins were compared with sarcomere mutation-negative HCM and nonfailing donors. Car

SUBMITTER: Sequeira V 

PROVIDER: S-EPMC3675884 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature