Figure 6. AAV-hTAZ reversal of established cardiac dysfunction in TAZ-CKO mice.

A. Experimental outline. TAZ-CKO mice with established heart dysfunction (FS<40%, ~ 2-month-old) were treated with medium or high doses of AAV, which were calibrated to transduce ~33% or ~70% CMs. B-C. Echocardiographic measurement of LV systolic function (B) and end diastolic diameter (C). Shading indicates standard deviation. Full statistical comparisons are provided in Online Data I. D. Cardiac hypertrophy, shown by the ratio of heart weight vs. bodyweight, was examined 3 months after treatment. E. Capillary immunoblotting of TAZ in heart extracts. AAV-hTAZ delivered human (hs) TAZ is longer than murine (mm) TAZ. F. Cardiac cardiolipin composition measured by mass spectrometry. G-H. Transcriptional correction of genes critical for mitochondrial function and heart failure program. n=3 per group. P values are indicated above bars. I-J. Cardiac fibrosis measured by sirius red/ fast green staining of cardiac samples at 4 months of age. Quantification is shown in J. Bar=200 μm. K-L. Cardiac apoptosis measured by TUNEL staining. Apoptotic CMs were identified with TNNI3 shown in insets. Percentage of TUNEL-positive CMs was quantified in L. Insects show TUNEL signal overlapping with TNNI3 and DAPI to identify CMs. Bar= 200 μm. Numbers indicate sections analyzed, from at least 3 different hearts per group. B, C: Repeated two way ANOVA followed by Tukey’s multiple comparison test. D, F, G, H, J: One way ANOVA test followed by Tukey’s multiple comparison test. L: Kruskal-Wallis with Dunn’s multiple comparisons test.