ADRIANA MACHADO SALDIBA DE LIMA

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LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina

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  • article 1 Citação(ões) na Scopus
    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 (vol 224, pg 66, 2012)
    (2013) MACHADO, R. M.; NAKANDAKARE, E. R.; QUINTAO, E. C.; CAZITA, P. M.; KOIKE, M. K.; NUNES, V. S.; FERREIRA, F. D.; AFONSO, M. S.; BOMBO, R. P.; MACHADO-LIMA, A.; SORIANO, F. G.; CATANOZI, S.; LOTTENBERG, A. M.
  • article 32 Citação(ões) na Scopus
    Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1-mediated reverse cholesterol transport
    (2013) MACHADO-LIMA, Adriana; IBORRA, Rodrigo T.; PINTO, Raphael S.; SARTORI, Camila H.; OLIVEIRA, Erika R.; NAKANDAKARE, Edna R.; STEFANO, Jose T.; GIANNELLA-NETO, Daniel; CORREA-GIANNELLA, Maria Lucia C.; PASSARELLI, Marisa
    Background We evaluated the effects of albumin isolated from control individuals and from patients with poorly controlled type 1 diabetes mellitus on macrophage gene expression and on reverse cholesterol transport. Methods Serum albumin was purified from control subjects (n = 12) and from patients with poorly controlled type 1 diabetes mellitus (n = 13). 14C-cholesterol-labelled J774 macrophages treated with albumin were employed to measure cholesterol efflux mediated by apo A-I, HDL3 or HDL2, the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyse gene expression. Several differentially expressed genes were validated by real-time reverse transcription-PCR using TaqMan Two Step RT-PCR. Results Levels of glycation-modified and (carboxymethyl)lysine-modified albumin were higher in diabetic patients than in control subjects. Apo A-I-mediated and HDL2-mediated cellular cholesterol efflux were impaired in macrophages treated with albumin from diabetic patients in comparison with control albumin-treated cells, which was attributed to the reduction in ABCA-1 protein content. Even in the presence of cholesterol acceptors, a higher level of intracellular lipid was observed in macrophages exposed to albumin from diabetic individuals in comparison with the control. The reduction in ABCA-1 content was associated with enhanced expression of stearoyl CoA desaturase 1 and decreased expression of janus kinase 2, which were induced by albumin from patients with type 1 diabetes mellitus. Conclusions (Carboxymethyl)lysine-modified albumin isolated from poorly controlled type 1 diabetic patients impairs ABCA-1-mediated reverse cholesterol transport and elicits intracellular lipid accumulation, possibly contributing to atherosclerosis.
  • article 18 Citação(ões) na Scopus
    Dual effect of advanced glycation end products in pancreatic islet apoptosis
    (2013) COSTAL, Flavia; OLIVEIRA, Erika; RAPOSO, Alexandre; MACHADO-LIMA, Adriana; PEIXOTO, Elisa; ROMA, Leticia; SANTOS, Laila; FARIA, Jose B. Lopes; CARPINELLI, Angelo Rafael; GIANNELLA-NETO, Daniel; PASSARELLI, Marisa; CORREA-GIANNELLA, Maria Lucia
    Background Loss of -cell function hastens deterioration of metabolic control in type 2 diabetes patients. Besides amyloid deposit and glucolipotoxicity, advanced glycation end products (AGEs) acting through their receptors (RAGE) seem to contribute to this process by promoting islet apoptosis. In order to investigate the role of AGEs in -cell deterioration, we evaluated the temporal and dose effects of AGE compounds on apoptosis rate, reactive oxygen species generation and expression of pro-apoptotic and anti-apoptotic genes in cultured islets. Methods Rat pancreatic islets were exposed or not for 24, 48, 72 and 96h to albumin modified by glycoaldehyde. Apoptosis, reactive oxygen species and superoxide content and NADPH oxidase activity were evaluated as well as RNA expression of the genes Ager (codes for RAGE), Bax, Bcl2 and Nfkb1. Results In 24 and 48h, glycoaldehyde elicited a decrease in apoptosis rate in comparison with the control condition concomitantly with a reduction in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In contrast, after 72 and 96h, glycoaldehyde promoted an increase in apoptosis rate concomitantly with an increase in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In 24h, glycoaldehyde elicited a decrease in the islet content of reactive oxygen species, whereas after 48 and 72h, it promoted an opposite effect, increasing superoxide generation. The NADPH oxidase inhibitor VAS2870 attenuated superoxide production, implicating NADPH oxidase as an important source of reactive oxygen species in islets exposed to AGEs. Conclusions Albumin modified by glycoaldehyde exerted a dual effect in cultured pancreatic islets, being protective against apoptosis after short exposure but pro-apoptotic after prolonged exposure.