title: Exercise preconditioning prevents MCT-induced right ventricle remodeling through the regulation of TNF superfamily cytokines.
abstract: BACKGROUND
  Exercise training has been recognized as a non-pharmacological therapeutic approach in several chronic diseases; however it remains to be tested if exercise preconditioning can positively interfere with the natural history of pulmonary arterial hypertension (PAH). This is important since the majority of these patients are diagnosed at advanced stages of the disease, when right ventricle (RV) impairment is already present.
  
  
  OBJECTIVE
  In the current study, we evaluated the preventive effect of exercise preconditioning on RV failure secondary to PAH, with a focus on the signaling pathways modulated by pro-inflammatory cytokines from TNF superfamily.
  
  
  METHODS
  We analyzed the RV muscle from adult male Wistar rats exposed to a 4-week treadmill exercise training or sedentary regime, prior to the administration of monocrotaline (MCT) to induce PAH or with saline solution (controls).
  
  
  RESULTS
  Data indicate that exercise preconditioning prevented cardiac hypertrophy and RV diastolic dysfunction. At a molecular level, exercise modulated the TWEAK/NF-κB signaling axis and prevented the shift in MHC isoforms towards an increased expression of beta-MHC. Exercise preconditioning also prevented the increase of atrogin-1 expression, and induced a shift of MMP activity from MMP-9 to MMP-2 activity.
  
  
  CONCLUSIONS
  Altogether, data support exercise as a preventive strategy for the management of PAH, which is of particular relevance for the familial form of PAH that is manifested by greater severity or earlier onset.
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Nogueira-Ferreira
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal. Electronic address: danielmgon@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreira-Gonçalves
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Silva
authors.affiliation: CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Portugal; Department of Cardiothoracic Surgery, Hospital of São João, Porto, Portugal.
authors.forename: Adelino
authors.initials: A
authors.lastname: Leite-Moreira
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: henriques.coelho@gmail.com.
authors.forename: Tiago
authors.initials: T
authors.lastname: Henriques-Coelho
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D009206:Myocardium / Q000378:metabolism*; D005082:Physical Exertion; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016278:Ventricular Function, Right / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016686:Monocrotaline
keywords: Exercise training; Heart failure; Pro-inflammatory cytokines; Pulmonary arterial hypertension; Right ventricle muscle