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Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin - contribution of glycemic control in diabetes mellitus

Grant number: 12/19112-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2013
Effective date (End): February 09, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Marisa Passarelli
Grantee:Adriana Machado Saldiba de Lima
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):14/05951-6 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin, BE.EP.PD   13/06800-9 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin, BE.EP.PD

Abstract

Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis independently of other risk factors. AGE induce the generation of oxygen reactive species (ROS) and inflammatory markers related to long term complications of DM. We recently demonstrated that advanced glycated albumin (AGE albumin) - isolated from poorly controlled DM patients - reduces the expression of the HDL receptor, ABCA-1, leading to cholesterol accumulation in macrophages. Our hypothesis is that the effects of AGE albumin in macrophages can be mediated by the interaction between the receptor for AGE (RAGE) and that the glycemic control can prevent alterations in lipid flux in that cells. Then, we intend to investigate the effect of RAGE silencing (by small interference RNA) and soluble RAGE in ROS generation, NF-kB activation, ABCA-1 expression and lipid accumulation in macrophages treated with albumin isolated from poorly glycemic control (HbA1c > 8%) and after metabolic adjustment (HbA1c < 7%). Findings will help to elucidate: 1) how glycemic control can contribute to the prevention of lipid accumulation in macrophages and 2) the participation of the AGE/RAGE axis in cellular lipid flux in DM that can contribute to therapeutic interventions.

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)
PINTO, PAULA R.; DA SILVA, KAROLLINE S.; IBORRA, RODRIGO T.; OKUDA, LIGIA S.; GOMES-KJERULF, DIEGO; FERREIRA, GUILHERME S.; MACHADO-LIMA, ADRIANA; ROCCO, DEBORA D. F. M.; NAKANDAKARE, EDNA R.; MACHADO, UBIRATAN F.; CORREA-GIANNELLA, MARIA L.; CATANOZI, SERGIO; PASSARELLI, MARISA. Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice. FRONTIERS IN PHYSIOLOGY, v. 9, MAY 8 2018. Web of Science Citations: 3.
IBORRA, RODRIGO TALLADA; MACHADO-LIMA, ADRIANA; OKUDA, LIGIA SHIMABUKURO; PINTO, PAULA RAMOS; NAKANDAKARE, EDNA REGINA; MACHADO, UBIRATAN FABRES; CORREA-GIANNELLA, MARIA LUCIA; PICKFORD, RUSSELL; WOODS, TOM; BRIMBLE, MARGARET A.; RYE, KERRY-ANNE; LU, RUI; YOKOYAMA, SHINJI; PASSARELLI, MARISA. AGE-albumin enhances ABCA1 degradation by ubiquitin-proteasome and lysosomal pathways in macrophages. JOURNAL OF DIABETES AND ITS COMPLICATIONS, v. 32, n. 1, p. 1-10, JAN 2018. Web of Science Citations: 2.
PINTO, PAULA RAMOS; FERRARETTO MOURA ROCCO, DEBORA DIAS; OKUDA, LIGIA SHIMABUKURO; MACHADO-LIMA, ADRIANA; CASTILHO, GABRIELA; DA SILVA, KAROLLINE SANTANA; GOMES, DIEGO JUVENAL; PINTO, RAPHAEL DE SOUZA; IBORRA, RODRIGO TALLADA; FERREIRA, GUILHERME DA SILVA; NAKANDAKARE, EDNA REGINA; MACHADO, UBIRATAN FABRES; CARDILLO CORREA-GIANNELLA, MARIA LUCIA; CATANOZI, SERGIO; PASSARELLI, MARISA. Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta. LIPIDS IN HEALTH AND DISEASE, v. 14, SEP 16 2015. Web of Science Citations: 10.

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