Fig. 3: MYC deletion in CFs ameliorates TAC-induced cardiac dysfunction.
a, Experimental scheme for generating cardiac-fibroblast-specific Myc KO mice. 0, day of TAC; 12 weeks, 12 weeks after TAC. b, Relative mRNA expression of Myc in the heart as measured via RT-qPCR. Data are shown as mean ± s.d. *P < 0.05; P < 0.001 (control (n = 10) versus WT-TAC (n = 7)), P = 0.13 (control versus KO-TAC (n = 11)); significance was determined using the two-sided Mann–Whitney test for mean comparisons. c, Representative images of the echocardiographic assessment of control and KO mice before and after TAC (20 weeks). d, The bar plots show cardiac function evaluated by echocardiography in control and KO mice before and after pressure overload (0–20 weeks). Data are shown as mean ± s.e. (TAC0w, control n = 5 and KO n = 6; TAC2w, 4 and 6; TAC4w, 5 and 6; TAC8w, 4 and 6; TAC12w, 4 and 5; TAC14w, 4 and 5; TAC16w, 4 and 5; TAC20W, 3 and 4). Tcf21 iCre-MYC flox mice were used for control. *P < 0.05; P = 0.018 (TAC8w), P = 0.018 (TAC12w), P = 0.007 (TAC14w), P = 0.018 (TAC16w), P < 0.001 (TAC20w); significance was determined using the two-sided Holm–Sidak test for mean comparisons. e, Relative mRNA expression of HF markers measured using RT-qPCR (n = 4 each). Data are shown as mean ± s.d. *P < 0.05; P = 0.029 (control versus WT-TAC, Nppa), P = 0.029 (WT-TAC versus KO-TAC, Nppa), P = 0.029 (control versus WT-TAC, Nppb), P = 0.029 (WT-TAC versus KO-TAC, Nppb), P = 0.029 (control versus WT-TAC, Myh7), P = 0.029 (WT-TAC versus KO-TAC, Myh7); significance was determined using the two-sided Mann–Whitney test for mean comparisons. f, The size of cardiomyocytes in control, WT-TAC and KO-TAC mice was evaluated using WGA staining. Quantitative analyses of the cell size in each mouse are shown (n = 100 cells each). The box plots show the median (center line) and first and third quartiles (box edges), while the whiskers go from each quartile to the minimum or maximum. *P < 0.05; P < 0.001 (control versus WT-TAC), P < 0.001 (WT-TAC versus KO-TAC); significance was determined using the two-sided Mann–Whitney test for mean comparisons. g, Fibrotic areas in the control, WT-TAC and KO-TAC mice were evaluated at the perivascular and interstitial regions via azan staining. Scale bars, 300 μm. Representative histological data and quantitative analyses of the fibrotic areas in each mouse are shown (n = 5 each). Data are shown as mean ± s.d. *P < 0.05; P = 0.0079 (control versus WT-TAC, perivascular), P = 0.84 (WT-TAC versus KO-TAC, perivascular), P = 0.0079 (control versus WT-TAC, interstitial), P = 0.69 (WT-TAC versus KO-TAC, interstitial); significance was determined using the two-sided Mann–Whitney test for mean comparisons. h, Kaplan–Meier survival curves for control and KO mice after TAC were compared using log-rank tests (n = 11 (control) and 10 (KO)).
