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Advanced glycation end products and renin-angiotensin system: impact on the development of atherosclerosis in dyslipidemic mice

Grant number: 12/19755-9
Support Opportunities:Regular Research Grants
Duration: January 01, 2013 - December 31, 2014
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marisa Passarelli
Grantee:Marisa Passarelli
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Sergio Catanozi ; Walcy Paganelli Rosolia Teodoro


Advanced glycation end products (AGE) are independently associated with the development of atherosclerosis. AGE diminish macrophage cholesterol efflux and increase the uptake of LDL favoring intracellular cholesterol accumulation. Besides, AGE induce the expression of angiotensinogen and AT-1 receptor in macrophages sharing with the angiotensin II receptors intracellular pathways that lead to the activation of NF-kB and its target genes, which is related to athesclerosis. It is possible that the role of AGE in atherogenesis could be related to enhanced expression of components of the renin-angiotensin system that has not been demonstrated in vivo. The aim of this project is to investigate the effect of intraperitoneal injection of advanced glycated albumin (AGE-albumin) alone or together with losartan treatment (inhibitor of AT-1 receptor) in arterial lipid and AGE accumulation and expression of inflammatory markers, angiotensin II, AT-1 receptor, receptor for AGE (RAGE) and oxidized LDL (LOX-1). Twelve week old male apoE knockout mice fed a chow diet will be randomically divided into 4 experimental groups: control (C) albumin , C albumin + ARB (losartan, 100 mg/L water); AGE-albumin and AGE + ARB. Mice will daily receive an intraperitoneal injection of control albumin or AGE-albumin (2 mg) during 30 days. Plasma concentration of total cholesterol, triglycerides, glucose, AGE, and anti AGE-antibody and blood pressure will be determined in basal and final periods. The expression of components of the renin-angiotensin system as well as LOX-1 and RAGE will be determined in aortic arch by immunofluorescence, lipid deposition by Oil Red O staining, inflammatory citokynes by ELISA and NF-kB mRNA by RT-PCR. Findings will help to elucidate the role of advanced glycation in the pathogenesis of atherosclerosis and its modulation by the renin-angiotensin system. (AU)

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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)
FUSCO, FERNANDA B.; GOMES, DIEGO J.; BISPO, KELY C. S.; TOLEDO, VERONICA P.; BARBEIRO, DENISE F.; CAPELOZZI, VERA L.; FURUKAWA, LUZIA N. S.; VELOSA, ANA P. P.; TEODORO, WALCY R.; HEIMANN, JOEL C.; et al. Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice. PLoS One, v. 12, n. 5, . (11/04631-0, 11/16164-7, 13/11084-0, 12/19755-9)
GOMES, DIEGO JUVENAL; VELOSA, ANA PAULA; OKUDA, LIGIA SHIMABUKURO; FUSCO, FERNANDA BUENO; DA SILVA, KAROLINNE SANTANA; PINTO, PAULA RAMOS; NAKANDAKARE, EDNA REGINA; CORREA-GIANNELLA, MARIA LUCIA; WOODS, TOM; BRIMBLE, MARGARET ANNE; et al. Glycated albumin induces lipid infiltration in mice aorta independently of DM and RAS local modulation by inducing lipid peroxidation and inflammation. JOURNAL OF DIABETES AND ITS COMPLICATIONS, v. 30, n. 8, p. 1614-1621, . (13/11084-0, 11/04631-0, 12/19755-9, 11/16164-7, 13/02854-7, 13/23392-1)

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