Of mice and men in acm:Novel models and biomarkers for arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a genetically inherited heart disease characterized by heart muscle cells dying and getting replaced by fibro-fatty tissue over time, leading to ventricular arrhythmias and sudden death in patients. In order to learn more about the disease mechanisms so that better therapies could be developed, we created 2 different mouse models that carry a genetic mutation that is equivalent to the one certain human patients have. We found that the mice are more resistant to developing ACM than human patients when they have 1 mutant copy of the gene, requiring additional stressors such as a second mutant copy or endurance exercise. We also created and characterized induced pluripotent stem cell cardiomyocytes (iPSC-CMs) from human patients with these mutations in order to compare them to the mouse models. Finally, in order to improve diagnosis of the disease, we identified a possible new circulating microRNA-based biomarker for ACM in human patients