p53 contributes to DOX-induced cardiac injury.

<p>A. Representative electron micrographs demonstrating cardiomyocyte injury and morphometric quantification of subcellular injury in cardiomyocytes in WT and p53^(−/−) mice. WT (a) and p53^(−/−) (b) mice treated with saline demonstrated normal ultrastructure of heart muscle with cardiomyocytes showing numerous mitochondria (M), prominent myofilaments (Myo) and lipids (Lip). WT (c) and p53^(−/−) (d) mice treated with DOX demonstrated the following pathologic changes: lysosomal degradation of mitochondria (asterisk), mitochondria with loss of cristae (arrow), peri-mitochondrial swelling (double arrow), disruption of mitochondrial membranes (arrowhead), and mitochondrial degeneration (d); scale bar, 1 µm. B. Pathologic changes were quantified for saline and DOX treated mice in the mitochondria and total cellular area (excluding nuclei). Quantification of damage for each specific compartment is expressed in the ratio of damaged area versus the total area. All graphs represent the Mean ± SEM for each group. *p<0.05 when compared with saline treated mice of the same genotype, and ^#p<0.05 when compared with WT mice treated with DOX. n = 6 or 7. C & D. Left ventricular function, assessed by percentage of ejection fraction (LV%EF) (C) and fractional shortening (LV%FS) (D), is expressed in percentage of change from basal levels caused by saline and DOX three days after injections for WT and p53^(−/−) mice. All bar graphs represent the Mean ± SEM for each group. ^#p<0.05 when compared to all three other groups. n = 6–11.