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. 2021 Jul 29;10(15):e021768. doi: 10.1161/JAHA.121.021768

Figure 4. Inhibition of ataxia telangiectasia and rad3‐related (ATR) kinase reduces pathological ventricular remodeling in Mybpc3−/− cardiomyopathy.

Figure 4

(A) Schematic illustration of ATR kinase inhibition from postnatal day (P) 4 to P7 with the drug AZD6738. (B) M‐mode echocardiography at P7 from control (Ctl) and Mybpc3−/− mice administered vehicle (Veh.) or 25 mg/kg per day AZD6738. Echocardiography assessment of interventricular septal thickness at end diastole (IVSd) (C), left ventricular posterior wall thickness at end diastole (LVPWd) (D), left ventricular internal diameter at end diastole (LVIDd) (E), and fractional shortening (FS) (F) in Ctl (n=5–7) and Mybpc3−/− (n=9–12) mice administered Veh. or AZD6738. Heart weight (HW) (G) and HW/body weight (BW) ratio (H) for Ctl (n=5–7) and Mybpc3−/− (n=9–12) mice administered Veh. or AZD6738. (I) Representative immunohistochemical staining with wheat‐germ agglutinin (green) and 4′,6‐diamidino‐2‐phenylindole (blue) of left ventricular (LV) tissue from Ctl and Mybpc3−/− mice administered Veh. or AZD6738. Bar=10 µm. (J) LV cross‐sectional area of Ctl (n=5) and Mybpc3−/− (n=5) mice administered Veh. or AZD6738. Minimum 50 cells/sample measured. (K) Western blot of p53 in myocardial tissue lysate from Mybpc3−/− administered Veh. or AZD6738. (L) Relative quantification of p53 protein expression from Mybpc3−/− administered Veh. (n=4) or AZD6738 (n=5) normalized to β‐actin. All results are shown as mean±SEM.