Abstract
Introduction: Arrhythmogenic cardiomyopathy (ACM) is a cardiac disease characterized by ventricular arrhythmia and a progressive replacement of myocardium by a fibro-fatty tissue. Our group, among others, showed that ACM Cardiac Stromal cells (CStCs) accumulate more lipids under adipogenic differentiation than control CStCs, which could be related to the disease pathophysiology1. Recent evidence also pointed toward a deregulation of mitochondrial activity and ROS signalling in ACM2,3. This work aimed to determine the activity of mitochondrial and ROS targeting compounds on ACM-CStCs lipid accumulation.
Material and Methods: Adipogenic differentiation of ACM-CStCs from one patient was triggered for 7 days in presence of mitochondrial and ROS targeting compounds (MedChem Express). Lipid accumulation was determined using the neutral lipid staining dye BODIPY 493/503, cell number measured using Hoechst counterstaining, and images acquired using a high-content imaging system (ImageXpress, Molecular Devices).
Results: On 407 compounds tested, around 25% demonstrated a capacity to reduce lipid accumulation in ACM-CStCs in which 24 compounds strongly decreased lipid accumulation by at least 50%.
Conclusion: This result confirms the importance of mitochondrial and ROS signalling in the adipogenic differentiation of ACM-CStCs and interrogates on their potential targeting for the treatment of ACM tissue remodelling.
1. Sommariva et al, 2016 – doi: 10.1093/eurheartj/ehv579
2. van Opbergen et al, 2019 – doi: 10.3389/fphys.2019.01496
3. Volani et al, 2022 – doi: 10.1111/jcmm.17396