Abstract
Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by lethal arrhythmias and a risk to sudden cardiac death. A hallmark feature of AC is the progressive replacement of the ventricular myocardium with fibro-fatty tissue, which can act as an arrhythmogenic substrate further exacerbating cardiac dysfunction. Therefore, identifying the processes underlying this pathological remodelling would help understand AC pathogenesis and support the development of novel therapies. In this review, we summarize our knowledge on the different models designed to identify the cellular origin and molecular pathways underlying cardiac fibroblast and adipocyte cell differentiation in AC patients. We further outline future perspectives and how targeting the fibro-fatty remodelling process can contribute to novel AC therapeutics.