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Influence of high intensity physical exercise on diaphragm muscle of rats with myocardial infarction-induced heart failure

Grant number: 14/16783-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2016
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Marina Politi Okoshi
Grantee:Aline Regina Ruiz Lima
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Chronic heart failure (HF) is characterized by a decreased exercise capacity with early fatigue and dyspnea. Several clinical and experimental studies have suggested that skeletal muscle abnormalities can contribute to these symptoms in heart failure patients. Changes of myosin heavy chain (MyHC) isoforms have been frequently observed in peripheral and respiratory muscles during heart failure. Pathophysiological mechanisms and intracellular signaling pathways involved on MyHCs alterations are not completely defined. Different intracellular pathways regulate skeletal muscle MyHC expression. The mitogen-activated protein kinase (MAPK) family is necessary for skeletal muscle mass and phenotype maintenance. This family can be modulated by several factors, such as inflammatory cytokines, especially tumoral necrosis factor-alpha (TNF-±), and oxidative stress. TNF-± is able to activated NF-ºB family, which is responsible for cellular processes like apoptosis, immunity, inflammation, and development/differentiation, and are expressed in skeletal muscle. Nowadays, there is no pharmacological therapy available to treat muscular alterations during heart failure. Physical exercise has been considered an important no-pharmacologic therapeutic strategy in preventing and rehabilitation in cardiovascular diseases. Physical exercise promote antioxidant enzymes raise and pro-oxidant enzymes reduction, showing an antioxidant action. Besides, exercise can modulate satellite cells activation. We did not find studies evaluating physical exercise effects on oxidative stress and MAPK and NF- ºB signaling pathways in diaphragm muscle. The aim of this study is to evaluated physical exercise on diaphragm muscle of infarcted rats. Animals will be submitted to aerobic high intensive interval physical exercise protocol, in treadmill, three times a week. Structural and functional cardiac evaluation will be accessed by echocardiography, before and after experimental period. MyHC isoforms will be analyzed by electrophoresis; MAPKs and NF-ºB pathways and TNF-± and Pax-7 proteins will be evaluated by western-blot; antioxidant enzymes will be analyzed by spectrometry; satellite cells activation will be verified by immunofluorescence; and TNF-± serum levels will be evaluated by ELISA. Statistical analysis: ANOVA, Pearson or Spearman, Goodman's test.