Impact of exercise training on cancer-induced cardiac dysfunction
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/15496 |
Resumo: | Cachexia is a complex syndrome characterized by severe weight loss frequently observed in cancer patients and associated with poor prognosis. Cancer cachexia is also related to modifications in cardiac muscle structure and metabolism leading to cardiac dysfunction. In order to better understand the cardiac remodeling induced by bladder cancer and the impact of exercise training after diagnosis on its regulation, we used an animal model of bladder cancer induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Healthy animals and previously BBN exposed animals were submitted to a training program in a treadmill at a speed of 20m/min, 60 min/day, 5 days/week during 13 weeks. At the end of the protocol, animals exposed to BBN presented a significant decrease of body weight, in comparison with control groups, supporting the presence of cancer cachexia. Morphological analysis of the cardiac muscle sections revealed the presence of fibrosis and a significant decrease of cardiomyocyte’s cross-sectional area, suggesting the occurrence of cardiac dysfunction associated with bladder cancer. These modifications were accompanied by heart metabolic remodeling characterized by a decreased fatty acid oxidation given by diminished levels of ETFDH and of complex II subunit from the respiratory chain. Exercise training promoted an increment of connexin 43, a protein involved in cardioprotection, and of c-kit, a protein present in cardiac stem cells. These results suggest an improved heart regenerative capacity induced by exercise training. In conclusion, endurance training seems an attractive non-pharmacological therapeutic option for the management of cardiac dysfunction in cancer cachexia. |
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Impact of exercise training on cancer-induced cardiac dysfunctionBioquímicaDoenças do coraçãoExercício físicoCancroCachexia is a complex syndrome characterized by severe weight loss frequently observed in cancer patients and associated with poor prognosis. Cancer cachexia is also related to modifications in cardiac muscle structure and metabolism leading to cardiac dysfunction. In order to better understand the cardiac remodeling induced by bladder cancer and the impact of exercise training after diagnosis on its regulation, we used an animal model of bladder cancer induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Healthy animals and previously BBN exposed animals were submitted to a training program in a treadmill at a speed of 20m/min, 60 min/day, 5 days/week during 13 weeks. At the end of the protocol, animals exposed to BBN presented a significant decrease of body weight, in comparison with control groups, supporting the presence of cancer cachexia. Morphological analysis of the cardiac muscle sections revealed the presence of fibrosis and a significant decrease of cardiomyocyte’s cross-sectional area, suggesting the occurrence of cardiac dysfunction associated with bladder cancer. These modifications were accompanied by heart metabolic remodeling characterized by a decreased fatty acid oxidation given by diminished levels of ETFDH and of complex II subunit from the respiratory chain. Exercise training promoted an increment of connexin 43, a protein involved in cardioprotection, and of c-kit, a protein present in cardiac stem cells. These results suggest an improved heart regenerative capacity induced by exercise training. In conclusion, endurance training seems an attractive non-pharmacological therapeutic option for the management of cardiac dysfunction in cancer cachexia.A caquexia é uma síndrome complexa caracterizada pela perda excessiva e involuntária de peso corporal comum em pacientes oncológicos e associada a um pior prognóstico. A caquexia associada ao cancro parece ainda estar relacionada com disfunção cardíaca que se caracteriza por alterações estruturais e metabólicas no músculo cardíaco. De forma a compreender melhor a remodelação cardíaca associada ao carcinoma urothelial e o impacto da prática de exercício físico após o diagnóstico na sua regulação, utilizou-se um modelo animal de carcinoma urothelial induzido por exposição a N-butil-N-(4-hidroxibutil)-nitrosamina (BBN) na bebida. Grupos de animais saudáveis e de animais previamente expostos ao BBN foram sujeitos a um programa de exercício em tapete rolante a 20m/min, 60 min/dia, 5 dias/semana durante 13 semanas. No final do protocolo, os animais expostos ao BBN apresentaram peso corporal significativamente menor, comparativamente aos animais controlo, confirmando a presença de caquexia. A análise morfométrica de seções de coração evidenciou fibrose e uma diminuição significativa da área de secção transversal dos cardiomiócitos, o que sugere a ocorrência de disfunção cardíaca associada ao carcinoma urotelial. Estas alterações morfológicas foram acompanhadas por uma remodelação metabólica do coração caracterizada pela diminuição da oxidação de ácidos gordos, dada pela diminuição dos níveis de ETFDH e de subunidade β do complexo II da cadeia respiratória. A prática de exercício físico promoveu o aumento de conexina 43, uma proteína com efeito cardioprotetor, e de c-kit, uma proteína presente em células estaminais do coração. Estes resultados sugerem um aumento da capacidade regenerativa do coração promovida pelo exercício físico. Em conclusão, a prática de exercício físico de endurance parece ser uma terapia não farmacológica adequada para o tratamento da disfunção cardíaca no contexto da caquexia associada ao cancro.Universidade de Aveiro2018-07-20T14:00:53Z2015-12-11T00:00:00Z2015-12-112017-12-04T12:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/15496TID:201573261engCarvalho, Dulce Isabel Macielinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T11:28:41Zoai:ria.ua.pt:10773/15496Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:50:52.339259Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Impact of exercise training on cancer-induced cardiac dysfunction |
title |
Impact of exercise training on cancer-induced cardiac dysfunction |
spellingShingle |
Impact of exercise training on cancer-induced cardiac dysfunction Carvalho, Dulce Isabel Maciel Bioquímica Doenças do coração Exercício físico Cancro |
title_short |
Impact of exercise training on cancer-induced cardiac dysfunction |
title_full |
Impact of exercise training on cancer-induced cardiac dysfunction |
title_fullStr |
Impact of exercise training on cancer-induced cardiac dysfunction |
title_full_unstemmed |
Impact of exercise training on cancer-induced cardiac dysfunction |
title_sort |
Impact of exercise training on cancer-induced cardiac dysfunction |
author |
Carvalho, Dulce Isabel Maciel |
author_facet |
Carvalho, Dulce Isabel Maciel |
author_role |
author |
dc.contributor.author.fl_str_mv |
Carvalho, Dulce Isabel Maciel |
dc.subject.por.fl_str_mv |
Bioquímica Doenças do coração Exercício físico Cancro |
topic |
Bioquímica Doenças do coração Exercício físico Cancro |
description |
Cachexia is a complex syndrome characterized by severe weight loss frequently observed in cancer patients and associated with poor prognosis. Cancer cachexia is also related to modifications in cardiac muscle structure and metabolism leading to cardiac dysfunction. In order to better understand the cardiac remodeling induced by bladder cancer and the impact of exercise training after diagnosis on its regulation, we used an animal model of bladder cancer induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Healthy animals and previously BBN exposed animals were submitted to a training program in a treadmill at a speed of 20m/min, 60 min/day, 5 days/week during 13 weeks. At the end of the protocol, animals exposed to BBN presented a significant decrease of body weight, in comparison with control groups, supporting the presence of cancer cachexia. Morphological analysis of the cardiac muscle sections revealed the presence of fibrosis and a significant decrease of cardiomyocyte’s cross-sectional area, suggesting the occurrence of cardiac dysfunction associated with bladder cancer. These modifications were accompanied by heart metabolic remodeling characterized by a decreased fatty acid oxidation given by diminished levels of ETFDH and of complex II subunit from the respiratory chain. Exercise training promoted an increment of connexin 43, a protein involved in cardioprotection, and of c-kit, a protein present in cardiac stem cells. These results suggest an improved heart regenerative capacity induced by exercise training. In conclusion, endurance training seems an attractive non-pharmacological therapeutic option for the management of cardiac dysfunction in cancer cachexia. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-12-11T00:00:00Z 2015-12-11 2017-12-04T12:00:00Z 2018-07-20T14:00:53Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/15496 TID:201573261 |
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http://hdl.handle.net/10773/15496 |
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TID:201573261 |
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eng |
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eng |
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embargoedAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de Aveiro |
publisher.none.fl_str_mv |
Universidade de Aveiro |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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