Figure 7. AKAP13-ΔGEF mutant mice undergo cardiac remodeling but have abnormal contractility in response to β-adrenergic-induced hypertrophy.

(A) Representative M-Mode echocardiogram images showed a thicker left ventricular wall in wild-type (WT) and AKAP13^ΔGEF/ΔGEF (ΔGEF) male mice treated with isoproterenol (Iso; 60 mg/kg per day for 13 days) than in those treated with PBS vehicle (Veh). Iso treatment increased the magnitude of contraction in WT mice but not in ΔGEF mice. The horizontal black scale bar is 200 ms; the vertical black scale bars are 1 mm. (B–E) Quantification of echocardiography data for left ventricle structural and functional changes in response to Iso treatment. Echocardiograms were recorded the day before mini-osmotic pumps were implanted for baseline levels (0) and after 13 days of Iso (+) or Veh (-) treatment. (B) Both WT and ΔGEF mice increased left ventricular (LV) mass to the same level with Iso treatment. (C) LV anterior wall thickness at diastole (LVAW;d) was increased to the same level in both WT and ΔGEF mice treated with Iso. (D) The percent of fractional shortening (FS) was greater in wild-type mice treated with Iso compared to baseline or Veh treatment. FS was not different in ΔGEF mice treated with Iso compared to baseline or Veh controls. However, ΔGEF mice treated with Iso tended to have reduced FS compared to wild-type controls. (E) The percent ejection fraction (EF) also was greater in wild-type mice treated with Iso than baseline or Veh treatment. Again, EF was not different in ΔGEF treated with Iso compared to baseline or Veh controls, but tended to be less than wild-type controls. The means and standard deviations are graphed in B–E for seven WT and nine ΔGEF mice at baseline (0), three WT and three ΔGEF mice with Veh treatment, and four WT and six ΔGEF mice with Iso treatment. One-way ANOVA and Bonferroni’s multiple comparison tests were conducted (Prism 5; GraphPad). †, p<0.10; *, p<0.05; **, p<0.01; ***, p<0.001.