Figure 4.
Effect of S107 on RyR2 remodeling and echocardiographic parameters in female LmnaH222P/H222P mice. (A) Immunoblot showing RyR2 immunoprecipitated from extracts of hearts of female WT mice and LmnaH222P/H222P mice treated with either placebo (LmnaH222P) or S107 (LmnaH222P + S107) and oxidation (DNP), PKA-catalyzed phosphorylation (pSer2808) and calstabin2 depletion. Samples are from mice at 30 weeks of age; treated mice received placebo or drug for 8 weeks. Migration of molecular mass standards are indicated to the left of the blot. (B–D) Quantification of associated calstabin2 (B), oxidized (C) and phosphorylated (D) RyR2 normalized to total RyR2 from WT mice and LmnaH222P/H222P mice treated with placebo (LmnaH222P) or S107 (LmnaH222P + S107). (E–H) Left ventricular end diastolic diameter (LVEDD) (E), left ventricular end systolic diameter (F), left ventricular FS and left ventricular EF (H) determined by echocardiography in WT mice and LmnaH222P/H222P mice treated with placebo (LmnaH222P) or S107 (LmnaH222P + S107). Values are means ± SEM (Control n = 5, LmnaH222P n = 9, LmnaH222P + S107 n = 8); *P < 0.05 LmnaH222P versus LmnaH222P + S107.