Tauroursodeoxycholic acid (TUDCA) prevents coxsackievirus B3 (CVB3)–induced cardiac C/EBP homologous protein (CHOP) activation and cardiomyocytes apoptosis in vivo. A, Representative images of CHOP staining in hearts of indicated treatment. Scale bar, 20 μm. B, TUDCA significantly reduced CHOP staining induced by CVB3 infection. Scale bar, 20 μm. C, Cardiomyocytes apoptosis was indicated by TUNEL staining. CVB3 infection caused increased cardiomyocytes apoptosis, whereas TUDCA administration prevented this effect. D, Western blot analysis of cardiac CHOP and cleaved caspase 3. E and F, CVB3 infection led to significantly induction of CHOP and cleaved caspase 3 expression in hearts, whereas TUDCA treatment markedly prevented these effects (control group: n=10; CVB3 group: n=6; CVB3+TUDCA: n=8; **P<0.01 vs control; ##P<0.01 vs CVB3).
Inhibition of endoplasmic reticulum stress restores cardiac Bcl-2/Bax ratio reduction induced by coxsackievirus B3 (CVB3) inoculation. A, Western blot analysis of cardiac Bcl-2 and Bax expression. B and C, CVB3 infection significantly reduced Bcl-2 expression and elevated Bax expression in hearts, while tauroursodeoxycholic acid (TUDCA) markedly blocked these effects (control group: n=10; CVB3 group: n=6; CVB3+TUDCA: n=8; **P<0.01 vs control; ##P<0.01 vs CVB3).
C/EBP homologous protein (CHOP) deficiency attenuates cardiomyocytes apoptosis induced by coxsackievirus B3 (CVB3) infection in vivo. A, CHOP deficiency reduced cardiomyocytes apoptosis after CVB3 infection as indicated by TUNEL staining. B, Western blot analysis of cardiac cleaved caspase 3 and atrial natriuretic peptide (ANP) expression. Compared with wild-type (WT) mice, CHOP deficiency significantly reduced ANP (C) and cleaved caspase 3 (D) expression induced by CVB3 infection. E, Western blot analysis of cardiac Bcl-2 and Bax expression. F, CHOP deficiency significantly prevented cardiac Bcl-2 reduction and Bax induction caused by CVB3 infection (WT group: n=10; WT+CVB3 group: n=5; CHOP−/−+CVB3 group: n=9; **P<0.01 vs WT; ##P<0.01 vs WT+CVB3).
Genetic knockout of C/EBP homologous protein (CHOP) reduces acute viral myocarditis severity and macrophage infiltration after coxsackievirus B3 (CVB3) infection. A, Representative histological (left) and macrophage marker F4/80 staining (right) of hearts with indicated intervention. Scale bar, 50 μm. Compared with wild-type (WT) mice, ablation of CHOP significantly reduced pathological score (B) and macrophage infiltration (C) induced by coxsackievirus B3 (CVB3) infection (WT group: n=10; WT+CVB3 group: n=5; CHOP−/−+CVB3 group: n=9; **P<0.01 vs WT; ##P<0.01 vs WT+CVB3). HE indicates hematoxylin and eosin.
Deficiency of C/EBP homologous protein (CHOP) reduces cardiac damage, prevents cardiac dysfunction, and promotes survival after coxsackievirus B3 (CVB3) infection. Compared with wild-type (WT) mice, CHOP deficiency markedly reduced cardiac troponin I (A) induction and heart weight/body weight (HW/BW) ratio (B) induced by CVB3 infection. C, CHOP ablation prevented reduction of dP/dt max and dP/dt min caused by CVB3 infection. D, Representative M-mode images of hearts with indicated treatment. CHOP deficiency reversed ejection fraction (EF; E) and fractional shortening (FS; F) decrease induced by CVB3 infection. G, CHOP deficiency promoted survival after CVB3 infection (WT group: n=10; WT+CVB3 group: n=5; CHOP−/−+CVB3 group: n=9; **P<0.01 vs WT; ##P<0.01 vs WT+CVB3).
