The DWORF micropeptide enhances contractility and prevents heart failure in a mouse model of dilated cardiomyopathy.

ABSTRACT: Calcium (Ca²⁺) dysregulation is a hallmark of heart failure and is characterized by impaired Ca²⁺ sequestration into the sarcoplasmic reticulum (SR) by the SR-Ca²⁺-ATPase (SERCA). We recently discovered a micropeptide named DWORF (DWarf Open Reading Frame) that enhances SERCA activity by displacing phospholamban (PLN), a potent SERCA inhibitor. Here we show that DWORF has a higher apparent binding affinity for SERCA than PLN and that DWORF overexpression mitigates the contractile dysfunction associated with PLN overexpression, substantiating its role as a potent activator of SERCA. Additionally, using a well-characterized mouse model of dilated cardiomyopathy (DCM) due to genetic deletion of the muscle-specific LIM domain protein

SUBMITTER: Makarewich CA 

PROVIDER: S-EPMC6202051 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature