Influência do treinamento físico sobre a função cardíaca, proliferação de cardiomiócitos e níveis de angiotensina-(1-7) e do receptor Mas miocárdicos em ratos com disfunção ventricular
Carregando...
Arquivos
Data
2017-02-23
Autores
Mota, Gustavo Augusto Ferreira [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Introdução: Nos últimos anos, investigadores têm demonstrado que há a possibilidade de estimular a proliferação de cardiomiócitos adultos. Atualmente, a comunidade científica está voltada para três principais estratégias para a regeneração cardíaca: uso de células tronco, inibição de genes que regulam o sistema de controle do ciclo celular e o aperfeiçoamento de mecanismos endógenos. Um exemplo de mecanismo endógeno é a estimulação de vias de sinalização que permite a reentrada dos miócitos no ciclo celular e sua posterior divisão. O treinamento físico (TF) é um fator estimulatório para a proliferação das células cardíacas por meio da angiotensina-(1-7) (Ang-(1-7)) via receptor Mas. Além disso, o TF promove cardioproteção e aumenta os níveis deste peptídeo em animais com sobrecarga pressórica. Existem evidências, recentes, que o TF promove proliferação de miócitos em diferentes modelos experimentais e atua sobre os níveis de Ang-(1-7) em corações disfuncionantes. Entretanto, não foram encontrados estudos que avaliaram, concomitantemente, os efeitos do TF sobre a função, níveis de Ang-(1-7) e receptor Mas miocárdicos e proliferação de cardiomiócitos em modelo de sobrecarga pressórica e deterioração da função cardíaca. Objetivo: Testar a hipótese que o TF atenua a queda do desempenho cardíaco, acarreta proliferação de cardiomiócitos e eleva os níveis de Ang-(1-7) e do receptor Mas miocárdicos em ratos com estenose aórtica supravalvar (EAo) e disfunção ventricular esquerda. Métodos: Ratos Wistar machos foram separados em dois grupos: controle operado (Sham) e EAo. Após 18 semanas do procedimento cirúrgico, os ratos EAo e Sham foram redistribuídos em 4 grupos e randomizados quanto a presença ou ausência do TF por 10 semanas; (Sham, n = 20), (EAo, n = 19), (ShamTF, n = 20) e (EAoTF, n = 15). A remodelação cardíaca foi caracterizada pelas análises estrutural e funcional por ecocardiograma na 18ª e 28ª semana e estudo macroscópico post mortem. A análise da capacidade funcional dos animais foi realizada pelo teste de esforço progressivo. A avaliação da proliferação dos cardiomiócitos, pelo conteúdo de DNA, foi feita por citometria de fluxo. O sistema renina angiotensina cardíaco foi analisado pela expressão proteica dos receptores Mas e AT1 por Western blot. Resultados: O TF promoveu melhoria na capacidade funcional dos animais Sham e EAo quanto a velocidade de exaustão, tempo total e distância percorrida. Ao iniciar o TF na 18º semana os animais EAo apresentavam disfunção diastólica, sistólica e hipertrofia ventricular esquerda concêntrica. Na 28ª semana, este grupo manteve o mesmo padrão de disfunção cardíaca. O TF não acarretou alteração na função diastólica e melhorou a estrutura e função sistólica dos animais EAo. Os animais ShamTF mostraram aumento da função sistólica comparados com o Sham. Não foram observadas diferenças entre os quatro grupos estudados em relação ao ciclo celular dos cardiomiócitos e expressão do receptor Mas no miocárdio. Houve diminuição da expressão do receptor AT1 no grupo EAo, e o TF não alterou este padrão no EAoTF. Conclusão: O treinamento físico melhorou a capacidade funcional e a função sistólica dos animais, sem repercussões benéficas sobre a função diastólica, proliferação de cardiomiócitos e expressão proteica do receptor Mas.
Introduction: In the last years, researchers have showed that it is possible to induce adult cardiomyocytes proliferation. Currently, the scientific community is focused on three main strategies for cardiac regeneration: stem-cell use, inhibition of genes that regulate cell-cycle control system and improvement of endogenous mechanisms. An example of endogenous mechanism is the stimulation of signaling pathways that allow the reentry of myocytes into the cell cycle and their posterior division. The physical training (PT) is a stimulatory factor for the proliferation of cardiac cells through angiotensin-(1-7) (Ang-(1-7)) via Mas-receptor. In addition, PT promotes heart protection and increases this peptide levels in animals with pressure overload. Recent evidences showed that PT promotes myocyte proliferation in distinct experimental models and acts on Ang-(1-7) levels in dysfunctional hearts. However, no studies were found that evaluated, concurrently, the effects of PT on cardiac function, myocardial levels of Ang-(1-7) and Mas receptor and cardiomyocyte proliferation in a model of pressure overload with deteriorated cardiac function. Objective: To test the hypothesis that PT attenuates the impairment in cardiac performance, leads to cardiomyocyte proliferation and increases myocardial Ang-(1- 7) and Mas-receptor levels in rats with supravalvar aortic stenosis (AS) and left ventricular dysfunction. Methods: Male Wistar rats were separated into two groups: operated control (Sham) and AS. After 18 weeks of the surgical procedure, AS and Sham rats were redistributed into four groups and randomized for the presence or absence of PT for 10 weeks; (Sham, n=20), (AS, n=19), (ShamPT, n=20) and (ASPT, n=15). Cardiac remodeling was characterized by structural and functional analysis by echocardiogram at the 18th and 28th week and by post-mortem macroscopic evaluation. The functional capacity of the groups was analyzed by the progressive treadmill running test. The cardiomyocyte proliferation was evaluated by DNA content using flow cytometry. The cardiac renin-angiotensin system was analyzed by protein expression of Mas and AT1 receptors by Western blot. Results: The PT improved the functional capacity of Sham and AS animals regarding the exhaust speed, total time and treadmill running distance. At the beginning of PT, at the18th week, the AS group presented diastolic and systolic dysfunction and concentric left ventricular hypertrophy. At the 28th week, AS group maintained the same pattern of cardiac dysfunction. The PT was not alter diastolic function and improved structure and systolic function in AS group. The ShamPT rats showed increased systolic function in relation to animals of Sham group. No differences were detected among the four groups regarding the cardiomyocyte cell cycle and the myocardial Mas-receptor expression. The expression of AT1 receptor was reduced in the AS group, and PT did not modify this pattern in ASPT group. Conclusion: The PT improved the functional capacity and systolic function of the rats, without beneficial repercussions on diastolic function, cardiomyocyte proliferation and protein expression of Mas receptor.
Introduction: In the last years, researchers have showed that it is possible to induce adult cardiomyocytes proliferation. Currently, the scientific community is focused on three main strategies for cardiac regeneration: stem-cell use, inhibition of genes that regulate cell-cycle control system and improvement of endogenous mechanisms. An example of endogenous mechanism is the stimulation of signaling pathways that allow the reentry of myocytes into the cell cycle and their posterior division. The physical training (PT) is a stimulatory factor for the proliferation of cardiac cells through angiotensin-(1-7) (Ang-(1-7)) via Mas-receptor. In addition, PT promotes heart protection and increases this peptide levels in animals with pressure overload. Recent evidences showed that PT promotes myocyte proliferation in distinct experimental models and acts on Ang-(1-7) levels in dysfunctional hearts. However, no studies were found that evaluated, concurrently, the effects of PT on cardiac function, myocardial levels of Ang-(1-7) and Mas receptor and cardiomyocyte proliferation in a model of pressure overload with deteriorated cardiac function. Objective: To test the hypothesis that PT attenuates the impairment in cardiac performance, leads to cardiomyocyte proliferation and increases myocardial Ang-(1- 7) and Mas-receptor levels in rats with supravalvar aortic stenosis (AS) and left ventricular dysfunction. Methods: Male Wistar rats were separated into two groups: operated control (Sham) and AS. After 18 weeks of the surgical procedure, AS and Sham rats were redistributed into four groups and randomized for the presence or absence of PT for 10 weeks; (Sham, n=20), (AS, n=19), (ShamPT, n=20) and (ASPT, n=15). Cardiac remodeling was characterized by structural and functional analysis by echocardiogram at the 18th and 28th week and by post-mortem macroscopic evaluation. The functional capacity of the groups was analyzed by the progressive treadmill running test. The cardiomyocyte proliferation was evaluated by DNA content using flow cytometry. The cardiac renin-angiotensin system was analyzed by protein expression of Mas and AT1 receptors by Western blot. Results: The PT improved the functional capacity of Sham and AS animals regarding the exhaust speed, total time and treadmill running distance. At the beginning of PT, at the18th week, the AS group presented diastolic and systolic dysfunction and concentric left ventricular hypertrophy. At the 28th week, AS group maintained the same pattern of cardiac dysfunction. The PT was not alter diastolic function and improved structure and systolic function in AS group. The ShamPT rats showed increased systolic function in relation to animals of Sham group. No differences were detected among the four groups regarding the cardiomyocyte cell cycle and the myocardial Mas-receptor expression. The expression of AT1 receptor was reduced in the AS group, and PT did not modify this pattern in ASPT group. Conclusion: The PT improved the functional capacity and systolic function of the rats, without beneficial repercussions on diastolic function, cardiomyocyte proliferation and protein expression of Mas receptor.
Descrição
Palavras-chave
Disfunção cardíaca, Treinamento físico, Ratos, Proliferação de cardiomiócitos, Receptor Mas