Truncation of titin's elastic PEVK region leads to cardiomyopathy with diastolic dysfunction.

ABSTRACT:

Rationale

The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region.

Objective

The purpose of this study was to investigate the contribution of titin's proline-glutamate-valine-lysine (PEVK) region to biomechanics and growth of the heart.

Methods and results

We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction,

SUBMITTER: Granzier HL 

PROVIDER: S-EPMC2785004 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature