Figure 6. Overexpression of mitochondrial creatine kinase (CKmito) maintains pro-/anti-hypertrophic transcription factor balance in TAC failing hearts.

Left ventricular (LV) tissue from WT, cardiac-specific CKmito overexpressing (CKmito^oe), or cardiac-specific myofibrillar CK overexpressing (CKmyofib^oe) sham or TAC hearts was isolated and analyzed. Representative immunoblots and summary of data showing expression levels of cMyc (Myc protooncogene protein) in: WT, CKmito^oe (A); or CKmyofib^oe (B) sham or TAC hearts normalized to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and presented as relative to the amount of protein detected in sham WT hearts (experimental replicates: n=10 (WT sham or WT TAC), n=11 (CKmito^oe sham), and n=8 (CKmito^oe TAC) (A); n=5 (WT sham or CKmyofib^oe sham) and n=6 (WT TAC or CKmyofib^oe TAC) (B). Data were tested for normality using the Kolmogorov-Smirnov test for normality and analyzed by non-parametric Kruskal-Wallis test, followed by pair-wise, two-sided multiple comparison analysis (Dunn method with Benjamini-Hochberg adjustment). The error bars represent ±SEM. (C) Scheme summarizing the attenuation of cardiac hypertrophy and dysfunction during pressure overload in CKmito^oe hearts. Abbreviations: OMM (outer mitochondrial membrane), IMM (inner mitochondrial membrane), Trx (thioredoxin), ROS (reactive oxygen species), Nrf2 (nuclear factor erythroid 2-related factor 2), CoQ (coenzyme Q), QH• (semiquinone), QH₂• (ubiquinol), CytC (cytochrome C), F₁F₀ (F₁F₀-ATP synthase), ANT (adenine nucleotide translocator), VDAC (voltage-dependent anion channel), CKmyofib (myofibrillar creatine kinase), CKmito (mitochondrial creatine kinase)