Hyperactivation of ATF4/TGF-β1 signaling contributes to the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy caused by DSG2 Variant.

ABSTRACT:

Background

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized with progressive cardiac fibrosis and heart failure. However, the exact mechanism driving the progression of cardiac fibrosis and heart failure in ACM remains elusive. This study aims to investigate the underlying mechanisms of progressive cardiac fibrosis in ACM caused by newly identified Desmoglein-2 (DSG2) variation.

Methods

We identified homozygous DSG2^F531C variant in a family with 8 ACM patients using whole-exome sequencing and generated Dsg2^F536C knock-in mice. Neonatal and adult mouse ventricular myocytes isolated from Dsg2^F536C knock-in mice were used. We performed functional, transcriptomic and mass spectrometry analyses to evaluate the mecha

SUBMITTER: Zhang B 

PROVIDER: S-EPMC11373413 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature