Characterising Shared and Specific Cell-Cell Communication in Cardiomyopathy Subtypes From Single-Cell...

Cardiomyopathy encompasses a diverse range of conditions characterised by extensive molecular heterogeneity, particularly the variations in cell-cell communication events such as ligand-receptor interactions and downstream signalling. Understanding the common and unique features of these intercellular interactions is crucial for advancing targeted treatments. We analysed single-cell RNA sequencing datasets from the ventricular regions of patients with arrhythmogenic cardiomyopathy (ACM), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and healthy donors (HD), as well as ischemic cardiomyopathy (ICM). Our analyses focused on cell type-specific disease preferences, differential gene expression, pathway enrichment and particularly cell-cell communication. We observed that inflammatory, autoimmune, angiogenesis, lymphangiogenesis and fibrotic extracellular matrix deposition are consistently enriched across all four disease subtypes, highlighting their universal significance in disease progression through intercellular interactions. Additionally, we identified subtype-specific pathways that reflect distinct intercellular communication patterns unique to each disease subtype: arrhythmia-associated pathways in ACM, chronic inflammation-related pathways in DCM, ECM remodelling pathways in HCM and ischaemic injury and recovery pathways in ICM.