The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy.

ABSTRACT:

Rationale

Mutations in the intercalated disc proteins, such as plakophilin 2 (PKP2), cause arrhythmogenic cardiomyopathy (AC). AC is characterized by the replacement of cardiac myocytes by fibro-adipocytes, cardiac dysfunction, arrhythmias, and sudden death.

Objective

To delineate the molecular pathogenesis of AC.

Methods and results

Localization and levels of selected intercalated disc proteins, including signaling molecules, were markedly reduced in human hearts with AC. Altered protein constituents of intercalated discs were associated with activation of the upstream Hippo molecules in the human hearts, in Nkx2.5-Cre:Dsp(W/F) and Myh6:Jup mouse models of AC, and in the PKP2 knockdown HL-1 myocytes (HL-1(PKP2:shRNA)). Level of active protein kinase C-α isoform, whic

SUBMITTER: Chen SN 

PROVIDER: S-EPMC3946717 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature