Influence of mTOR pathway on cardiac remodeling induced by retinoic acid

• Grant number: 12/21186-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2013
• End date: February 28, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Leonardo Antonio Mamede Zornoff
• Grantee: Renata Aparecida Candido da Silva
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cardiac remodeling involves several morphologic alterations due to cardiac injury. It is accepted that remodeling plays a critical role in the pathology of ventricular dysfunction. Therefore, studies are analyzing the use of different strategies to attenuate cardiac remodeling in different experimental and clinical models.Vitamin A is a potential modulator of cardiac remodeling. In previous study, retinoic acid supplementation induced hypertrophy, with increased left ventricular diameter, without collagen accumulation, with preservation of systolic function. There are two interpretations. Firstly, the results could be associated with early stage of pathologic alterations, like compensated volume overload. On the other hand, the results are also similar to physiologic process, like exercise training. Thus, the effects of retinoic acid in normal hearts remain to be elucidated. The mTOR (Mammalian Target of Rapamycin) complex is responsible for several physiologic functions. It is found in two complex, mTORC1 (mediated by S6K) and mTORC2 (mediated by AKT e NFkB). Importantly, mTORC1 is involved in pathologic process, whereas mTORC2 is involved in physiologic conditions. Therefore, the study of the mTOR complex might elucidate the effects of retinoic acid in the heart. In this manner, this project pretends study the association among AKT, NFkB, S6K, and the remodeling process induced by retinoic acid.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, RENATA A. C.; GONCALVES, ANDREA F.; DOS SANTOS, PRISCILA P.; RAFACHO, BRUNA; CLARO, RENAN F. T.; MINICUCCI, MARCOS F.; AZEVEDO, PAULA S.; POLEGATO, BERTHA F.; ZANATI, SILMEIA G.; FERNANDES, ANA ANGELICA; et al. Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 43, n. 4, p. 1449-1459, 2017. (12/21186-2)