Abstract
Arrhythmogenic cardiomyopathy (ACM) is a genetic-based cardiac disease accompanied by severe ventricular arrhythmias and a progressive substitution of the myocardium with fibrofatty tissue. ACM is often associated with sudden cardiac death. Due to the reduced penetrance and variable expressivity, the presence of a genetic defect is not conclusive, thus complicating the diagnosis and prognosis of ACM. Moreover, no conventional therapies exist for fibrofatty substitution. Over the past years not only human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) but also primary cardiac stromal cells (CStCs) have demonstrated to be appropriate in vitro tools to model ACM pathophysiology. Studies on ACM cells showed dysregulated metabolic and redox status when compared to healthy control (CTRL) cells. However, despite these efforts there is still a substantial lack of information regarding the whole metabolomic profile of ACM patients and ACM-derived cells. The aim of the present study was to investigate the metabolic profiles of ACM patients compared to CTRLs. In addition, we also performed an untargeted metabolic profiling of ACM and CTRL CStCs supernatants and pellets. The targeted Biocrates AbsoluteIDQ® p180 assay was used on plasma samples. Our data indicate that the plasma metabolome of ACM patients show signs of endothelium damage and impaired nitric oxide (NO), fat, and energy metabolism. Preliminary results on CStCs also highlight the involvement of redox mechanisms in the ACM pathogenesis.