Rita Nogueira-Ferreira1, Daniel Moreira-Gonçalves2, Ana Filipa Silva3, José Alberto Duarte4, Adelino Leite-Moreira5, Rita Ferreira6, Tiago Henriques-Coelho7. 1. QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. 2. 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. 3. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. 4. CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal. 5. 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. 6. QOPNA, Department of Chemistry, University of Aveiro, Aveiro, Portugal. 7. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: henriques.coelho@gmail.com.
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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Rita Nogueira-Ferreira; Rita Ferreira; Ana Isabel Padrão; Paula Oliveira; Manuel Santos; Andreas N Kavazis; Rui Vitorino; Daniel Moreira-Gonçalves Journal: J Physiol Biochem Date: 2019-10-16 Impact factor: 4.158
Authors: Akylbek Sydykov; Argen Mamazhakypov; Aleksandar Petrovic; Djuro Kosanovic; Akpay S Sarybaev; Norbert Weissmann; Hossein A Ghofrani; Ralph T Schermuly Journal: Front Physiol Date: 2018-05-23 Impact factor: 4.566
Authors: Cristine Schmidt; José A Bovolini; Nádia Gonçalves; Francisco Vasques-Nóvoa; Maria do Amparo Andrade; Mário Santos; Adelino Leite-Moreira; Tiago Henriques-Coelho; José Alberto Duarte; Daniel Moreira-Gonçalves Journal: Porto Biomed J Date: 2020-09-16