Exercise-induced adaptations of cardiac redox homeostasis and remodeling in heterozygous SOD2-knockout mice.

A reduced expression of the manganese-dependent superoxide dismutase (SOD2) is characterized by increased cardiac oxidative stress. Oxidative stress has also been described in situations of physical exercise. We investigated the influence of physical exercise (EX; treadmill 1 h/day at 15 m/min, 5 days/wk, at an angle of 5° for a duration of 8 wk) on cardiac function [heart frequency (HF), echocardiography, morphometry], oxidative stress [reactive oxygen species (ROS)], and antioxidative defence capacity (peroxiredoxin 1-6) in male SOD2-knockout (SOD2_EX) and wild-type mice (WT_EX) compared with untrained age-matched animals (WT_CON; SOD2_CON). In SOD2_CON, heart weight, cardiomyocyte diameter, and cardiac ROS were significantly larger and peroxiredoxin isoforms 4-6 lower than in WT_CON. The vessel-to-cardiomyocyte ratio, cardiac VEGF-concentration, and cardiac function were similar in SOD2_CON and WT_CON. Both groups tolerated the exercise protocol well. In WT, exercise significantly increased vessel-to-cardiomyocyte ratio and ROS-generation and downregulated peroxiredoxin isoforms 4-6 and VEGF generation. The vessel-to-cardiomyocyte ratio, cardiac VEGF concentration, and cardiac ROS were not altered in SOD2_EX compared with SOD2_CON, but a significant upregulation of cardiac peroxiredoxin 1 and 4 was observed. Similar to the result observed in WT_EX, peroxiredoxin 3 was upregulated in SOD2_EX. Chronic exercise shifted the (mal)adaptive hypertrophic into a compensated dilated cardiac phenotype in SOD2_EX. In conclusion, downregulation of SOD2 induces a maladaptive cardiac hypertrophy. In this situation, physical exercise results in a further deterioration of cardiac remodeling despite an upregulation of the antioxidative defense system.