Exercise training impacts cardiac mitochondrial proteome remodeling in murine urothelial carcinoma

Abstract

Cardiac dysfunction secondary to cancer may exert a negative impact in patients' tolerance to therapeutics, quality of life, and survival. The aim of this study was to evaluate the potential therapeutic effect of exercise training on the heart in the setting of cancer, after diagnosis. Thus, the molecular pathways harbored in heart mitochondria from a murine model of chemically-induced urothelial carcinoma submitted to 8-weeks of high intensity treadmill exercise were characterized using mass spectrometry-based proteomics. Data highlight the protective effects of high intensity exercise training in preventing left ventricle diastolic dysfunction, fibrosis, and structural derangement observed in tumor-bearing mice. At the mitochondrial level, exercise training counteracted the lower ability to produce ATP observed in the heart of animals with urothelial carcinoma and induced the up-regulation of fatty acid oxidation and down-regulation of the biological process "cardiac morphogenesis". Taken together, our data support the prescription of exercise training after cancer diagnosis for the management of disease-related cardiac dysfunction. ; This work was supported by the Portuguese Foundation for Science and Technology (FCT), European Union, QREN, FEDER and COMPETE for funding the QOPNA (UID/QUI/00062/2013), CIAFEL (UID/DTP/00617/2013), iBiMED (UID/BIM/04501/2013), Unidade de Investigação Cardiovascular (UID/IC/00051/2013) research units and the research projects (EXPL/DTP-DES/1010/2013, FCOMP-01-0124-FEDER-041115, POCI-01-0145-FEDER-007628). R.V. and D.M.G. are supported by individual fellowship grants (IF/00286/2015 and SFRH/BPD/90010/2012, respectively). The authors would like to thank Celeste Resende for their assistance in sample preparation for morphological analysis.