Figure 2. BET inhibition delays DCM in PLN^R9C mice.

(A) Experimental protocol. (B) Representative M-mode images of WT and PLN^R9C vehicle- or JQ1-treated mice at 18 weeks of age. Echo, echocardiography. (C–F) Echocardiographic assessment of mice treated with JQ1 or vehicle demonstrates progressive systolic dysfunction and negative LV remodeling in PLN^R9C mice that was significantly blunted by JQ1 (n = 14 PLN^R9C, n = 7 WT mice per group; ANOVA corrected for multiple hypothesis testing). Representative images demonstrating cardiac fibrosis: (G) Masson’s trichrome–stained LV sections from WT and PLN^R9C hearts and (H) false-color images of fibrosis identified by Keyence microscope software (yellow, fibrosis; box, enlarged region). As JQ1 had no effect on fibrosis in WT, a single representative WT image is shown. Scale bar in G: 200 μm. Original magnification in H, ×10.(I) Quantification of scar area demonstrated severe fibrosis in PLN^R9C vehicle-treated hearts at 20-weeks of age that was markedly blunted by JQ1 (n = 3 mice, 36 images from n = 4 levels from apex to base for each mouse). Boxes, IQR; whiskers, 1.5× IQR; black line, median; notches, SD, circles, extreme outlier values).