Adipogenic Signaling Promotes Arrhythmia Substrates before Structural Abnormalities in TMEM43 ARVC.

ABSTRACT: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of desmosomal and structural proteins that is characterized by fibro-fatty infiltrate in the ventricles and fatal arrhythmia that can occur early before significant structural abnormalities. Most ARVC mutations interfere with β-catenin-dependent transcription that enhances adipogenesis; however, the mechanistic pathway to arrhythmogenesis is not clear. We hypothesized that adipogenic conditions play an important role in the formation of arrhythmia substrates in ARVC. Cardiac myocyte monolayers co-cultured for 2-4 days with mesenchymal stem cells (MSC) were derived from human-induced pluripotent stem cells with the ARVC5 TMEM43 p.Ser358Leu mutation. The TMEM43 mutation in myocyte co-cultures alone had no significan

SUBMITTER: Vasireddi SK 

PROVIDER: S-EPMC9604824 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature