title: Endurance training prevents TWEAK but not myostatin-mediated cardiac remodelling in cancer cachexia.
abstract: 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.
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Padrão
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreira-Gonçalves
authors.affiliation: CITAB, Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
authors.affiliation: CITAB, Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Teixeira
authors.affiliation: CITAB, Department of Veterinary Sciences, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Faustino-Rocha
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Helguero
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Vitorino
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute of Oncology, Porto, Portugal.
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
authors.affiliation: QOPNA, School of Health Sciences, University of Aveiro, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal. Electronic address: ritaferreira@ua.pt.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002100:Cachexia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000074049:Cytokine TWEAK; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D015674:Mammary Neoplasms, Animal / Q000150:complications*; D008565:Membrane Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D014508:Urea / Q000737:chemistry / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D000074049:Cytokine TWEAK; D008565:Membrane Proteins; D055435:Myostatin; C497771:Tnfsf12 protein, rat; D048069:Tumor Necrosis Factors; D014508:Urea
keywords: Mammary tumours; Physical activity; Pro-inflammatory cytokines; Wasting