Ionising radiation induces persistent alterations in the cardiac mitochondrial function of C57BL/6 mice 40 weeks after local heart exposure

Abstract Background and purpose Radiotherapy of thoracic and chest-wall tumours increases the long-term risk of radiation-induced heart disease. The aim of this study was to investigate the long-term effect of local heart irradiation on cardiac mitochondria. Methods C57BL/6 and atherosclerosis-prone ApoE −/− mice received local heart irradiation with a single X-ray dose of 2Gy. To investigate the low-dose effect, C57BL/6 mice also received a single heart dose of 0.2Gy. Functional and proteomic alterations of cardiac mitochondria were evaluated after 40weeks, compared to age-matched controls. Results The respiratory capacity of irradiated C57BL/6 cardiac mitochondria was significantly reduced at 40weeks. In parallel, protein carbonylation was increased, suggesting enhanced oxidative stress. Considerable alterations were found in the levels of proteins of mitochondria-associated cytoskeleton, respiratory chain, ion transport and lipid metabolism. Radiation induced similar but less pronounced effects in the mitochondrial proteome of ApoE −/− mice. In ApoE −/− , no significant change was observed in mitochondrial respiration or protein carbonylation. The dose of 0.2Gy had no significant effects on cardiac mitochondria. Conclusion This study suggests that ionising radiation causes non-transient alterations in cardiac mitochondria, resulting in oxidative stress that may ultimately lead to malfunctioning of the heart muscle.