June 2013 Researcher of the Month - Adriana Machado-Lima, PhD
I am a dietitian and I developed my PhD project in the Lipids Laboratory (LIM 10) from the Endocrinology Program of Faculty of Medical Sciences, University of Sao Paulo, Sao Paulo, Brazil. In this project we demonstrated that advanced glycated albumin - isolated from poorly controlled diabetic patients - reduces the cholesterol efflux mediated by Apo A-I and HDL subfractions and decreases the ABCA-1 expression leading to lipid accumulation in macrophages, possibly contributing to atherosclerosis.
Currently, I am a Postdoctoral fellow and I have joined the Diabetes Research Program in order to study the mechanisms of RAGE involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin.
1. Costal F, Oliveira E, Raposo A, Machado-Lima A, Peixoto E, Roma L, Santos L, Lopes Faria J, Carpinelli AR, Giannella-Neto D, Passarelli M, Correa-Giannella ML. Dual effect of advanced glycation end products (AGEs) in pancreatic islet apoptosis. Diabetes Metab Res Rev. 2013 Jan 12.
2. Machado-Lima A, Iborra RT, Pinto RS, Sartori CS, Oliveira ER, Nakandakare ER, Stefano JT, Giannella-Neto D, Corrêa-Giannella MLC, Passarelli M. Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1 mediated reverse cholesterol transport. Diabetes Metab Res Rev. 2013 Jan; 29(1):66-76.
3. Machado RM, Nakandakare ER, Quintao EC, Cazita PM, Koike MK, Nunes VS, Ferreira FD, Afonso MS, Bombo RP, Machado-Lima A, Soriano FG, Catanozi S, Lottenberg AM. Omega -6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr -KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids. Atherosclerosis. 2012 Sep; 224(1):66-74.
4. de Souza Pinto R, Castilho G, Paim BA, Machado-Lima A, Inada NM, Nakandakare ER, Vercesi AE, Passarelli M. Inhibition of macrophage oxidative stress prevents the reduction of ABCA -1 transporter induced by advanced glycated albumin. Lipids. 2012 May; 47(5):443-50.
5. Iborra RT, Machado-Lima A, Castilho G, Nunes VS, Abdalla DS, Nakandakare ER, Passarelli M. Advanced glycation in macrophages induces intracellular accumulation of 7-ketocholesterol and total sterols by decreasing the expression of ABCA-1 and ABCG-1. Lipids Health Dis. 2011 Sep 29; 10:172.
6. Machado AP, Pinto RS, Moysés ZP, Nakandakare ER, Quintão EC, Passarelli M. Aminoguanidine and metformin prevent the reduced rate of HDL-mediated cell cholesterol efflux induced by formation of advanced glycation end products. Int J Biochem Cell Biol. 2006 Mar; 38(3):392-403.
7. Machado AP, Costa Rosa LF, Seelaender MC. Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration. Cell Tissue Res. 2004 Dec; 318(3):503-14.
Machado-Lima A. Glycated Albumin Isolated from Uncontrolled Type 1 and Type 2 Diabetes Mellitus Patients Impairs Cell Cholesterol Removal and Induces Lipid Accumulation in Macrophages. Complications of Diabetes and Obesity, 2009, Vancouver, Canada.
Poster Presentations in Symposiums and Conferences
1. Machado-Lima A, Iborra RT, Pinto RS, Sartori CH, Oliveria ER, Nakandakare ER, Côrrea-Giannela MLC, Passarelli M. In: Type 2 Diabetes, Insulin Resistance and Metabolic Dysfunction, 2011, Keystone, Colorado. Type 2 Diabetes, Insulin Resistance and Metabolic Dysfunction. Keystone Symposia on Molecular and Cellular Biology, 2011, p.363.
2. Machado-Lima A, Iborra RT, Pinto RS, Sartori CH, Oliveria ER, Stefano JT, Nakandakare ER, Giannella-Neto D, Côrrea-Giannela MLC, Passarelli M. AGE-Albumin induces intracelular lipid accumulation by modifying the expression of genes involved in macrophage reverse cholesterol transport and cholesterol homeostasis In: 79º EAS congress, 2011, Gothenburg. Atherosclerosis Supplements. 2011, v.12, p.35-36.
3. Iborra RT, Machado-Lima A, Castilho G, Nunes VS, Nakandakare ER, Abdalla, DSP, Passarelli M. Glycoxidation impairs the HDL-mediated oxysterols efflux and induces sterol accumulation in macrophages In: 79º EAS congress, 2011, Gothenburg. Atherosclerosis Supplements. 2011, v.12 p.46.
4. Costal FSL, Oliveria ER, Amaral ASR, Machado-Lima A, Passarelli M, Wajchenberg BL, Giannella-Neto D, Côrrea-Giannela MLC. Dual effect of advanced glycation end productis (AGEs) in pancreatic islet apoptosis and the protective role of benfotiamine and MitoQ In: 70th Scientific Sessions of American Diabetes Association, 2010, Orlando. Diabetes Supplement. 2010, v.59, p.A444.
5. Castilho G, Sartori CH, Machado-Lima A, Nakandakare ER, Santos CX, Laurindo FR, Passarelli M. Endoplasmic reticulum stress inhibition prevents the ABCA-1 reduction in glycated albumin-treated macrophages In: The 78th Congress of the European Atherosclerosis Society (EAS), 2010, Hamburgo. Atherosclerosis Supplements. 2010, v.11, p.136.
6. Machado JT, Pinto RS, Castilho G, Machado-Lima A, Iborra RT, Rocha, JC, Carreiro AB, Nakandakare ER, Catanozi S, Passarelli M. Reverse cholesterol transport is not influenced by HDL composition or the reduced macrophage ABCG-1 expression in chronic kidney disease rats In: The 78th Congress of the European Atherosclerosis Society (EAS), 2010, Hamburgo. Atherosclerosis Supplements. 2010, v.11, p.71.
7. Carreiro, AB, Machado-Lima A, Iborra, Rodrigo Talada, Pinto, Raphael de Souza, Castilho, Gabriela, Rocha, JC, Machado, JT, Nakandakare, Edna Regina, Catanozi, S, Passarelli, Marisa. Serum Albumin isolated from diabetic or uremic rats enhances the mouse peritoneal macrophages LDL uptake In: The 78th Congress of the European Atherosclerosis Society (EAS), 2010, Hamburgo. Atherosclerosis Supplements. 2010, v.11, p.111.
8. Machado-Lima A, Iborra RT, Sartori CH, Nakandakare ER, Côrrea-Giannela MLC, Passarelli M. Serum albumin isolated from uncontrolled diabetes mellitus patients impairs the reverse cholesterol transport In: 70th Scientific Sessions of American Diabetes Association, 2010, Orlando. Diabetes Supplement. 2010, v.59, p.A240.
9. Machado-Lima A, Pinto RS, Holanda C, Iborra RT, Nakandakare ER, Côrrea-Giannela MLC, Passarelli M. In vivo glycated albumin impairs the removal of cholesterol induncing lipid accumulation in macrophages. In: XV International Symposium on Atherosclerosis, 2009, Boston. Atherosclerosis Supplement, 2009, v. 10, p. P1133.
10. Pinto, RS, Paim BA, Machado-Lima A, Nakandakare ER, Vercesi AE, Passarelli M. Reduced abca-1 expression in macrophages submitted to glycoxidation relates to an increased mitochondrial and nadph oxidase-mediated oxidative stress and to a diminished mitochondrial respiratory chain activity. In: XV International Symposium on Atherosclerosis, 2009, Boston. Atherosclerosis Supplements, 2009, v. 10, p1139.
11. Pinto, PS, Machado-Lima A, Paim, BA, Vercesi AE, Nakandakare ER, Quintão ECR, Passarelli M. intracellular oxidative stress induced by advanced glycated albumin reduces abca-1, abcg-1 and increases rage and cd-36 expression. in: 67th scientif sessions of american diabetes association, 2007, chicago. diabetes (suppl), 2007, v. 56, p724-p.
12. Pinto RS, Machado AP, Philipson PB, Okuda LS, Nakandakare ER, Quintão ECR, Passarelli M. Glycated Albumin Slows Down the Cell Cholesterol Efflux Rate by Simultaneously Reducing the HDL Binding to Its Receptor and Inducing Intracellular Glycoxidation. In: 65th Scientific Sessions of The American Diabetes Association, 2005, San Diego. Diabetes, 2005, v53, p764-P-764-P.
13. Machado AP, Pinto RS, Nakandakare ER, Quintão ECR, PassarellI M. Impairment of the HDL-mediated Cell Cholesterol Efflux Rate by Advanced Glycated Albumin is Reversed by Aminoguanidine. In: 64th Scientific Sessions of The American Diabetes Association, 2004, Orlnado. Diabetes. New Jersey: American Diabetes Association, 2004, v.53, p194-194.
Advanced glycation end products (AGE) are elevated in diabetes and predict the development of atherosclerosis independently of other risk factors. Understanding these mechanisms will help to elucidate the consequences of the AGE/RAGE axis in cellular lipid flux in diabetes and as a result this can contribute to developing new therapeutic interventions.
As a dietitian I know it is difficult for diabetic patients to achieve good glycemic control. Therefore, my plan is to investigate if after metabolic adjustment, glycemic control can contribute to the prevention of lipid accumulation in macrophages. This could be another method for diabetic patients to take care of themselves.
Furthermore, I would like to pursue more possibilities of studying and investigating cardiovascular complications in diabetes and also to have the opportunity to exchange experiences with other researchers and encourage the training of new scientists.