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 Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2013
• End date: February 09, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marisa Passarelli
• Grantee: Adriana Machado Saldiba de Lima
• Host 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

(7)

(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)

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.; et al. 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. (12/19112-0, 13/26256-1, 16/15603-0, 12/12088-7, 13/02854-7, 15/21072-5)

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; et al. 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. (12/19112-0, 11/04631-0, 12/12088-7, 11/15153-1, 12/04831-1, 12/18724-2, 13/02854-7)

MACHADO-LIMA, ADRIANA; LOPEZ-DIEZ, RAQUEL; IBORRA, RODRIGO TALLADA; PINTO, RAPHAEL DE SOUZA; DAFFU, GURDIP; SHEN, XIAOPING; NAKANDAKARE, EDNA REGINA; MACHADO, UBIRATAN FABRES; CORREA-GIANNELLA, MARIA LUCIA CARDILLO; SCHMIDT, ANN MARIE; et al. RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 19, OCT 2020. (12/19112-0, 15/21072-5, 13/06800-9, 18/00172-0, 13/26256-1, 12/12088-7, 14/05951-6, 16/15603-0)

MACHADO-LIMA, A.; TALLADA IBORRA, R.; SHIMABUKURO OKUDA, L.; SOUZA PINTO, R.; REGINA NAKANDAKARE, E.; CORREA-GIANNELLA, M. L. C.; PASSARELLI, M.. ADEQUATE GLYCEMIC CONTROL PREVENTS CHOLESTEROL EFFLUX IMPAIRMENT AND LIPID ACCUMULATION IN MACROPHAGES INDUCED BY ADVANCED GLYCATED ALBUMIN. ATHEROSCLEROSIS, v. 275, p. 1-pg., 2018-08-01. (12/19112-0, 15/21072-5)

MACHADO-LIMA, ADRIANA; OLIVEIRA, ERIKA R.; IBORRA, RODRIGO T.; CASTILHO, GABRIELA; NAKANDAKARE, EDNA R.; CORREA-GIANNELLA, MARIA LUCIA C.; TRALDI, PIETRO; PORCU, SIMONA; ROVERSO, MARCO; LAPOLLA, ANNUNZIATA; et al. Characterization of Glycated Albumin Isolated From Poorly Controlled Diabetic Patients and Its Role in Macrophage Cholesterol Efflux. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, v. 34, p. 2-pg., 2014-05-01. (12/19112-0)

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.; et al. 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. (12/19112-0, 16/15603-0, 13/11084-0, 12/12088-7, 11/15153-1, 12/18724-2, 13/02854-7, 14/07617-6, 15/21072-5)

MINANNI, CARLOS ANDRE; MACHADO-LIMA, ADRIANA; IBORRA, RODRIGO TALLADA; OKUDA, LIGIA SHIMABUKURO; PINTO, RAPHAEL DE SOUZA; MELLO SANTANA, MONIQUE DE FATIMA; DE ARAUJO LIRA, AECIO LOPES; NAKANDAKARE, EDNA REGINA; CARDILLO CORREA-GIANNELLA, MARIA LUCIA; PASSARELLI, MARISA. Persistent Effect of Advanced Glycated Albumin Driving Inflammation and Disturbances in Cholesterol Efflux in Macrophages. NUTRIENTS, v. 13, n. 10, OCT 2021. (17/18545-4, 12/19112-0, 16/15603-0, 12/12088-7, 18/00172-0, 15/21072-5)