Figure 2. Cardiac-specific overexpression of mitochondrial creatine kinase (CKmito) improves in vivo cardiac energetics and attenuates pathologic remodeling in failing murine hearts.

Tissues were isolated from WT and cardiac-specific CKmito overexpressing (CKmito^oe) mice. (A) Expression levels of CKmito were normalized to total protein and presented as relative to the amount of CKmito detected in WT hearts (experimental replicates: n=4 (WT LV or atria), n=5 (CKmito LV or atria)). Representative transverse in vivo ¹H MRI of mice at the mid-left ventricle showing (B) WT sham, (C) CKmito^oe sham, (D) WT TAC, and (E) CKmito^oe TAC. In vivo cardiac ³¹P MRS and MRI measures of (F) ATP and (G) phosphocreatine (PCr) levels; (H) CK forward pseudo-first-order rate constant (K_f); (I) CK flux; (J) left ventricular (LV) mass; (K) end-diastolic volume (EDV); (L) end-systolic volume (ESV); and (M) ejection fraction (EF) for WT or CKmito^oe mice with or without TAC (experimental replicates: n=5 (WT sham), n=8 (WT TAC or CKmito^oe sham), and n=7 (CKmito^oe TAC) for F-I and n=5 (WT sham), n=12 (WT TAC), n=8 (CKmito^oe sham), and n=7 (CKmito^oe TAC) for J-M), (N) LV mass and (O) EDV for WT or cardiac-specific myofibrillar CK overexpressing (CKmyofib^oe) mice with or without TAC (experimental replicates: n=6 (WT sham or CKmyofib^oe sham), n=9 (WT TAC), n=7 (CKmyofib^oe TAC)); and (P) LV mass, and (Q) EDV for WT or CKmito^oe mice following chronic isoproterenol (ISO) or saline infusion (experimental replicates: n=5 (WT saline or CKmito^oe saline), n=7 (WT ISO), and n=10 (CKmito^oe ISO)). Graphs show data points for individual mice. Data were tested for normality using the Kolmogorov-Smirnov test for normality and analyzed by two-tailed Student’s t-test (A), two-way ANOVA followed by Tukey’s post-hoc multiple comparison tests (F-K, M, O-Q), or Wilcoxon signed rank test followed by pair-wise, two-sided multiple comparison analysis (Dwass, Steel, Crichlow-Fligner Method) (L, N). The error bars represent ±SEM.