Figure 4. SB216763 treatment improves myocardial injury and cardiac function in JUP^2157del2 and Dsg2^mut/mut mice.

(A) Representative images of ventricular myocardia from JUP^2157del2 and Dsg2^mut/mut mice treated with vehicle (Veh) or SB216763 (SB2). Myocardia were immunostained with H&E, Masson's trichrome (MTC), and TUNEL. Scale bar: 50 μm. Images are representative of n ≥ 4/genotype (white arrows, TUNEL-positive nuclei). (B) Percentage fibrosis and TUNEL-positive nuclei in hearts from SB2- and Veh-treated mutant mice. Fibrosis: n = 4/genotype; TUNEL: n = 4 for WT and Dsg2^mut/mut mice and n = 6 for WT and JUP^2157del2 mice. Mean ± SEM. P < 0.05 for WT vs. ACM mice using 2-tailed paired t test. (C) Quantitative ECG telemetry analysis of SB2-treated JUP^2157del2 mice exhibited decreased bouts of single and >2 premature ventricular complexes. Representative ECG telemetry tracing from a vehicle-treated JUP^2157del2 mouse. Mean ± SEM. P < 0.05 for SB2-treated JUP^2157del2 (n = 16) vs. Veh-treated JUP^2157del2 (n = 6) mice using 2-tailed t test with equal variance. (D) Echocardiography and ECG telemetry analysis of Veh- and SB2-treated Dsg2^mut/mut mice. In box-and-whisker plots, horizontal bars indicate the medians, boxes indicate 25th to 75th percentiles, and whiskers indicate 10th and 90th percentiles. Mean ± SEM, n = 4/genotype/treatment. *P < 0.05 for SB2-treated Dsg2^mut/mut vs. Veh-treated Dsg2^mut/mut mice using 2-way ANOVA with Tukey's post-hoc analysis.