Resveratrol action on proteoglycans membrane present in heart muscle in an animal model of diabetic cardiomyopathy

• Grant number: 12/20262-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2013
• End date: July 31, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Celia Maria Cassaro Strunz
• Grantee: Celia Maria Cassaro Strunz
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Antonio de Padua Mansur ; Maria Claudia Costa Irigoyen

Abstract

In rats with type 1 diabetes induced by streptozotocin (STZ) alterations in proteoglycans, sindecan-4 and glipican-1 in cardiac tissue occurs concomitantly to the installation of diastolic dysfunction, early event culminating in diabetic cardiomyopathy. In this study, however, was not established whether the changes in contractile function of the hearts can be attributed directly to changes in these proteoglycans levels or occur in a parallel way or if it is a consequence of the involvement of other important metabolic pathways, such as sirtuins (SIRT). Several substances can stimulate the metabolic pathway of sirtuins, being resveratrol (RSV) the most important. The improvement of cardiac function by treatment with RSV has already been demonstrated, which could involve the proteoglycans, which level could stop rising after the treatment with this flavonoid.Objective: To establish a link between the levels of SIRT1, an enzyme activated by RSV, and proteoglycans in an experimental model of chronic disease in an attempt to elucidate some of the mechanisms involved in the outbreak of this disease.Materials and Methods: During 8 weeks 32 male Wistar rats will be studied being divided into 4 groups of 8 animals each: control group I, group II + RSV control (normal rats), group III - type II diabetes (STZ-induced nicotinamide + ) and group IV-RSV + type II diabetes. The assessment of diabetes will be made through the measurement of glucose, triglycerides and free fatty acids and insulin resistance test. Gene expression of SIRT-1-glipican 1 sindecan-4, FGF 2, and RAGE in heart tissue will be quantified by real-time PCR. The proteins concentrations: glypican-1, syndecan-4 SIRT-1, FGF-2 in the heart muscle will be analyzed by Western blot. The location of the proteins in cardiac tissue will be made by immunohistochemistry and immunogold labelling in Electron Microscopy. The rats will be subjected to pulsatile arterial pressure records for analysis of cardiovascular autonomic control and evaluation of cardiac function using high resolution echocardiography. (AU)

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)

CRUZ, PAULA L.; MORAES-SILVA, IVANA C.; RIBEIRO, AMANDA A.; MACHI, JACQUELINE F.; DE MELO, MARCELO DANTAS TAVARES; DOS SANTOS, FERNANDO; DA SILVA, MAIKON BARBOSA; STRUNZ, CELIA MARIA CASSARO; CALDINI, ELIA GARCIA; IRIGOYEN, MARIA-CLAUDIA. Nicotinamide attenuates streptozotocin-induced diabetes complications and increases survival rate in rats: role of autonomic nervous system. BMC Endocrine Disorders, v. 21, n. 1, JUN 28 2021. (12/20262-7)

CASSARO STRUNZ, CELIA MARIA; ROGGERIO, ALESSANDRA; CRUZ, PAULA LAZARA; PACANARO, ANA PAULA; CURY SALEMI, VERA MARIA; BENVENUTI, LUIZ ALBERTO; MANSUR, ANTONIO DE PADUA; IRIGOYEN, MARIA CLAUDIA. Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 40, p. 219-227, FEB 2017. (12/20262-7)