Full text
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| Author(s): |
Rodrigo Wagner Alves Souza
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2014-00-00 |
| Examining board members: |
Anselmo Sigari Moriscot;
Francis Lopes Pacagnelli;
Maria Julia Marques;
Denise Vaz de Macedo
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| Advisor: | Maeli Dal Pai |
| Abstract | |
Heart failure (HF) is associated with exercise intolerance due to early fatigue and dyspnea. These symptoms are related to atrophy and changes in the skeletal muscle phenotype. Aerobic exercise training is proposed and accepted to minimize muscle abnormalities in HF. Thus, elucidate the molecular mechanisms related to cardiac and skeletal muscle alterations in this disease may help in designing therapeutic interventions and for targeting specific training programs. The aim of if the aerobic training performed during the transition from cardiac hypertrophy to HF would alter the cardiac structure, function and molecular expression, in addition to gene and protein levels of components that mediate atrophic and hypertrophic pathways in skeletal muscle of rats with HF submitted to aerobic training. Three- to four-week-old male Wistar rats weighing 90¿100 g were submitted to aortic stenosis surgery. A total of 8 age-matched control animals underwent left thoracotomy without clip placement (Sham group). At 18 weeks after surgery, when the aortic stenosis animals (AS) presented ventricular dysfunction as measured by echocardiography, the AS animals were redistributed into 2 groups: aortic stenosis untrained (AS-UN, n = 8), in which the group of AS rats remained untrained over a 10-week period, and aortic stenosis exercise training (AS-ET, n = 8), in which the AS rats that were subjected to 10 weeks of aerobic ET. After 28 weeks, all 3 groups underwent another echocardiogram and were then euthanized. The heart was removed, and the atria and ventricles were separated to fibrosis and gene expression analysis. The soleus and plantaris muscles were harvested to subsequent analysis of muscle fibers morphometry, bichemistry, protein and gene. The evaluation of gene expression and protein levels was performed by real-time PCR (RT-qPCR) and Western blotting, respectively. The serum was used for analysis of IGF-1 and TNF-? by ELISA. At the end of the experiment, At 28 weeks, the AS-UN group presented HF signs in conjunction with soleus and plantaris muscle atrophy and an increase in the expression of TNF-?, NF?B, MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented in association with a prevention of muscle wasting and a decrease in atrophy promoters. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR) were not observed. Nevertheless, in the plantaris muscle, high PGC1? levels were maintained by ET. Thus, the ability of aerobic training performed during the transition from cardiac hypertrophy to HF to attenuate cardiac function was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors but through anti-catabolic activity, presumably caused by PGC1? action. These findings indicate the therapeutic potential of aerobic training to block HF-induced muscle atrophy by counteracting the increased catabolic state (AU) | |