Influência da via mTOR no processo de remodelação cardíaca induzida pelo ácido retinóico

• Ano de defesa: 2015
• Autor(a) principal: Silva, Renata Aparecida Candido da [UNESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Remodelação ventricular; Retinóides; Tretinoína; Rato como animal de laboratorio; Ventricular remodeling; Tretinoin
• Link de acesso: http://hdl.handle.net/11449/139338; http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/13-05-2016/000864208.pdf

The process of cardiac remodeling can be influenced by several factors including mechanical, genetics and biochemical, that emphasize the importance of retinoic acid (RA). Evidence suggests that the RA is essential in the embryonic period and in the post embryonic development, it can trigger/modulate cardiac hypertrophy. However it is unclear whether the cardiac hypertrophy induced by RA is physiological or pathological. The main objective of the study was to investigate the involvement of mTOR pathway through the study of Akt, NFκB, S6K and PI3K in its total and phosphorylated forms. Secondary objectives were to evaluate the involvement of MAPKs (JNK / ERK) and the consequences of energy metabolism and oxidative stress in rats supplemented with RA. For this we used 80 rats divided into 4 groups: the control group (C, n = 20) received standard diet; AR1 (n = 20), AR2 (n = 20) and AR3 (n = 20) received 0.3; 5 and 10mg AR/kg diet respectively. After two months the animals were submitted to echocardiographic study, study of isolated heart and euthanized for collection of biological material. The variables evaluated were the percentage of collagen, sectional area of myocytes, transverse diameter of myocytes, protein by western blot, oxidative stress and enzymes of energy metabolism. Statistical analysis was performed through 1- way ANOVA complemented by recommended tests. To assess the doseresponse, a test for linear trend was used. In our study we observed that there was a dose-dependent effect on the diameter of the left atrium, being higher in group C and lower group AR3; cardiomyocyte hypertrophy without collagen accumulation; activation of MAPKs by increasing the expression of JNK; reduction of pyruvate dehydrogenase; the β-hydroxyacyl-CoA dehydrogenase, ATP synthase, complex I and complex II compared to group C; and an increase in lipid hydroperoxide and catalase also when compared to group C. Thus it can be concluded that the ...