Fig. 3

ChATKD hearts show an elevation in heart failure markers, morphological changes in the ventricle, and enhanced reactive oxygen species with DNA damage. a The ANP and BNP mRNA levels are both increased in ChATKD hearts (P = 0.014 and 0.043, respectively). Furthermore, the ANP protein expression levels are upregulated in the ChATKD hearts (P = 0.032). b Masson’s trichrome staining displays the ChATKD hearts possessing characteristic fibrosis (black arrowheads) in the ventricles. Scale bar: 50 μm. c The expression levels of glucose utilization-related factors, i.e., HIF-1α (P = 0.007), pAkt/Akt (P = 0.010), and Glut4 (P = 0.014) are lower in the ChATKD hearts than in the control hearts. Cardiac ATP levels are lower in ChATKD mice than in control mice (P = 0.012). d Reciprocally, the PDK4 expression levels are higher in the ChATKD hearts (P = 0.019); in contrast, the PGC-1 (P = 0.028) and VEGF levels (P = 0.019) are lower in the ChATKD hearts. e ChATKD mice upregulate gluconeogenesis in the liver. Hepatic mRNA levels of G6Pase (P = 0.005) and PEPCK (P = 0.006) are higher in ChATKD mice than in control mice, and each protein expression also shows the same increasing trend (P < 0.05); however, this is in contrast to the ChAT tg mice, which reciprocally downregulate gluconeogenesis in the liver (G6Pase, P = 0.0008; PEPCK, P < 0.0001). f VEGF immunoreacted endothelial cells (white arrowheads) appear reduced in the ChATKD hearts. Immunoreactivity of von Willebrand factor (black arrowheads) is attenuated in ChATKD hearts. Scale bar: 50 μm. CD34 signal levels in the heart are also attenuated in ChATKD mice compared with those in control mice. Scale bar: 10 μm. g ChATKD hearts are more exposed to augmentation of the ROS production through MDA (P = 0.019), nitrotyrosine stain intensity associated with the increased protein expression levels (P = 0.026), and γ-H2A expression (P = 0.027), but reciprocally attenuated SOD activity (P = 0.033), than the control hearts. Scale bar: 20 μm