Fig 2: Upregulation of ADAMTS2 alleviates the effect of TGF-ß1 on cardiac fibroblasts. (A) The mRNA expression of Adamts2 in CFs and NRCMs was determined by RT-qPCR. * P < 0.05. (B) The protein expression of Adamts2 in CFs and NRCMs was determined western blot. * P < 0.05. (C) The mRNA expression of Adamts2 in TGF-ß1 treated CFs at different time points. * P < 0.05 vs. the 0h group. (D) The protein expression of Adamts2 in TGF-ß1 treated CFs at different time points. * P < 0.05 vs. the 0h group. (E) The overexpression of Adamts2 in CFs was determined by western blot. (F) The migration ability of CFs was showed by wound healing assay. (G) The relative migration distance of Adamts2 overexpressed CFs. (H) The cell viability was calculated by CCK-8. * P < 0.05 vs. the Control group. # P < 0.05 vs. the TGF-ß group. (I) The expression of a-SMA and Col1 were determined by western blot. * P < 0.05 vs. the Control group. # P < 0.05 vs. the TGF-ß group. (J) The downregulation of Adamts2 in CFs was determined by western blot. (K) The migration ability of CFs was showed by wound healing assay. (L) The relative migration distance of Adamts2 downregulated CFs. (M) The cell viability was calculated by CCK-8. * P < 0.05 vs. the Control group. # P < 0.05 vs. the TGF-ß group. (N) The expression of a-SMA and Col1 were determined by western blot. * P < 0.05 vs. the Control group. # P < 0.05 vs. the TGF-ß group.

Fig 3: Six hub genes and corresponding transcriptional factors. (A) t-SNE plot showing the expression characteristic of the six hub genes in the control and heart failure samples. (B) Heatmap showing the expression of six hub genes in each cell type. (C) Relative mRNA expression of the six hub genes in the 2w TAC model. * P < 0.05. (D) Heatmap showing the expression of differentially expressed transcriptional factors in each cell type. (E) Transcriptional factor and hub gene regulatory network. (F) Correlation diagram between MYC and ADAMTS2.

Fig 4: MYC transcriptionally regulates ADAMTS2. (A) Three predicted binding sites of the MYC protein in the ADAMTS2 promoter region are shown. (B) Boxplot showing the expression of MYC mRNA in GSE141910. * P < 0.05. (C, D) Co-transfection of the mutant ADAMTS2 promoter recombinant vector and the MYC expression vector in 293 cells is verified using dual luciferase reporter gene assays. * P < 0.05 versus the oe-NC group. (E) Binding of MYC to the ADAMTS2 promoters is tested using ChIP assays. * P < 0.05 versus the IgG antibody group.

Fig 5: Boxplots of the sixteen genes in hypertrophic cardiomyopathy dataset (GSE141910). (A) FLNC; (B) CCL2; (C) TANC2; (D) ADAMTS2; (E) MIDN; (F) PRRC1; (G) LDLR; (H) SOCS3; (I) DYNLL1; (J) RND3; (K) NOTCH2; (L) MRC2; (M) DLG1; (N) DOCK7; (O) EGR1; (P) OTUD1. ns P > 0.05, * P < 0.05, ** P < 0.01, *** P < 0.001.