Endurance training prevents TWEAK but not myostatin-mediated cardiac remodelling in cancer cachexia

• Published in: Archives of biochemistry and biophysics 2015-02, Vol.567, p.13-21
• Main Authors: Padrão, Ana Isabel, Moreira-Gonçalves, Daniel, Oliveira, Paula A., Teixeira, Catarina, Faustino-Rocha, Ana I., Helguero, Luísa, Vitorino, Rui, Santos, Lúcio Lara, Amado, Francisco, Duarte, José Alberto, Ferreira, Rita
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Animals; Apoptosis Regulatory Proteins - metabolism; Cachexia - complications; Cachexia - metabolism; Cachexia - pathology; Cachexia - physiopathology; Cytokine TWEAK; Female; Heart - drug effects; Heart - physiopathology; Mammary Neoplasms, Animal - complications; Mammary tumours; Membrane Proteins - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Myostatin - metabolism; Physical activity; Physical Conditioning, Animal; Pro-inflammatory cytokines; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Tumor Necrosis Factors - metabolism; Urea - chemistry; Urea - pharmacology; Wasting
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2014.12.026

•Mammary tumours induce cardiac fibrosis and myofiber disorganization.•Cancer-induced cardiac dysfunction seems to be mediated by TWEAK and myostatin.•Exercise prevents cancer-related increase of serum and cardiac TWEAK.•Exercise prevents cancer-induced cardiac proteolysis and fibrosis. Strategies to prevent tumour burden-induced cardiac remodelling that might progress to heart failure are necessary to improve patients’ health outcomes and tolerability to cancer therapies. Exercise has been suggested as a measure to prevent cardiac damage; however, its effectiveness on regulating cardiac remodelling secondary to cancer was never addressed. Using an animal model of mammary tumorigenesis, we studied the impact of 35weeks of endurance training on heart, focusing on the signalling pathways modulated by pro-inflammatory and wasting cytokines. The cardiac fibrosis and myofiber disorganization induced by tumour burden was paralleled by the increase of myostatin and TWEAK with the activation of signalling pathways involving Smad-3, NF-κB, TRAF-6 and atrogin-1. The activation of Akt/mTOR was observed in heart from rats with tumours, for which contributed the extracellular matrix. Endurance training prevented the increase of serum and cardiac TWEAK promoted by cancer, as well as the activation of NF-κB, TRAF6, atrogin-1 and p70S6K in heart. Data highlight the impact of exercise in the modulation of signalling pathways activated by wasting cytokines and the resulting outcomes on heart adaptation. Future studies focused on the cellular pathways underlying cardiac remodelling will assist in the development of exercise programs targeting cancer-related cardiac alterations.