Fig. 2: Disturbed intercellular crosstalk in hypertrophied hearts.

a, Circos plots visualizing ligand–receptor interactions. Interactions between the different cell types were analyzed using CellPhoneDB to analyze cells from healthy hearts (left) and patients with AS (right). Incoming signals are shown in red. Outgoing signals are shown in the colors assigned to the respective cell type. The thickness of the lines indicates the number of interactions. b, Total ligand–receptor interactions in hearts of healthy individuals versus patients with AS. c, Total ligand–receptor interactions in cardiomyocytes of hearts of healthy individuals versus those with AS. d, Cardiomyocyte ligand–receptor interactions with other cardiac cell types. Shown are incoming signals (number of interactions) with a ligand expressed by any other cell type and the respective receptor expressed by cardiomyocytes. e,f, Representative cardiomyocyte ligand–receptor interaction scores calculated with CellPhoneDB are shown. e, Downregulated pathways from cardiomyocyte interactions with endothelial cells in hearts of patients with AS (left, of 32 total significant interactions) and upregulated pathways from those in hearts of patients with AS (right, of 25 total significant interactions). Direction of communication is indicated by arrows. f, Downregulated pathways from cardiomyocyte interactions with fibroblasts in hearts of patients with AS (left, of 23 total significant interactions) and upregulated pathways from those in hearts of patients with AS (right, of 25 total significant interactions). ANGPT, angiopoietin; COL, collagen; EGFR, epidermal growth factor receptor; FGFR1, FGF receptor 1; FN1, fibronectin 1; GAS6, growth arrest-specific 6; IGF1, insulin-like growth factor 1; IGF1R, IGF1 receptor; JAG1, jagged canonical Notch ligand 1; LRP1, LDL receptor-related protein 1; NCAM1, neural cell adhesion molecule 1; NRP2, neuropilin 2; PLXNB2, plexin B2; PTN, pleiotrophin; PTPRS, protein tyrosine phosphatase receptor type S; SEMA, semaphorin; TGFBR3, transforming growth factor β receptor 3. Statistical analysis for interaction pathways was assessed using the CellPhoneDB package in R (e,f).