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. 2018 Jun 5;27(17):3060–3078. doi: 10.1093/hmg/ddy215

Figure 4.

Figure 4.

Phosphorylated (Thr25) cofilin-1 induces cardiac dysfunction. (A) Immunoblots showing cofilin-1, phosphorylated (Thr25) cofilin-1, cofilin-2 and gapdh in protein extracts from hearts of Lmna+/+ (Lmna WT) transduced with AAV vectors encoding cofilin-1; NT indicates not transduced. Representative from three independent repeats. (B) Immunoblot illustrating the effect of AAV expressing cofilin-1 construct on the amount of G-actin and F-actin and the calculated F/G actin ratio in hearts from mice; NT indicates not transduced. Data are represented as means±SEM (n=3; ***P<0.0005) from three independent repeats. (C) Immunoblots showing cofilin-1, phosphorylated (Thr25) cofilin-1, cofilin-2 and gapdh in protein extracts from hearts of LmnaH222P/H222P (Lmna H222P) transduced with AAV vectors encoding the indicated proteins; NT indicates not transduced. Representative from three independent repeats. (D) Immunoblot illustrating the effect of AAV expressing cofilin-1 constructs on the amount of G-actin and F-actin and the calculated F/G actin ratio in hearts from mice transduced with AAV vectors encoding the indicated proteins; NT indicates not transduced. Data are represented as means±SEM (n=3; *P<0.05, **P<0.005) from three independent repeats. (E) Graph showing left ventricular fraction shortening (FS) in 3-month-old (prior injection of AAV) and 6-month-old male transduced Lmna WT mice and Lmna H222P mice (see Table 2 for details). The central line represents the median, the box limits the interquartile range and the whiskers the minimum and maximum (*P<0.05, ***P<0.0005). (F) Expression of Col1a2, Myh7 and NppA mRNAs in hearts from 6-month-old male Lmna+/+ mice (Lmna WT) transduced with AAV expressing cofilin-1 or not transduced (NT). Data are represented as means±SEM (n=4; *P<0.05, **P <0.005, ***P <0.0005). (G) Expression of Col1a2, Myh7 and NppA mRNAs in hearts from 6-month-old male LmnaH222P/H222P mice (Lmna H222P) transduced with AAV expressing cofilin-1 or AAV expressing cofilin-1-T25A. Data from Lmna H222P mice not transduced (NT) are showed for comparison. Data are represented as means±SEM (n=4; *P<0.05, **P <0.005).