MARISA PASSARELLI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- The effects of exercise on lipid profile in systemic lupus erythematosus and healthy individuals: a randomized trial(2015) BENATTI, Fabiana Braga; MIOSSI, Renata; PASSARELI, Marisa; NAKANDAKARE, Edna R.; PERANDINI, Luiz; LIMA, Fernanda Rodrigues; ROSCHEL, Hamilton; BORBA, Eduardo; BONFA, Eloisa; GUALANO, Bruno; PINTO, Ana Lucia de SaThe aim of the present study was to evaluate the effects of an exercise training program on lipid profile and composition of high-density lipoprotein (HDL) subfractions in systemic lupus erythematosus (SLE) patients and healthy controls. A 12-week, randomized trial was conducted. Thirty-three physically inactive SLE patients were randomly assigned into two groups: trained (SLE-TR, n = 17) and non-trained (SLE-NT, n = 16). A gender-, BMI-, and age-matched healthy control groups (C-TR, n = 11) also underwent the exercise program. Subjects were assessed at baseline (Pre) and 12 weeks after the 3-month exercise training program (Post) for lipid profile (HDL, low-density lipoprotein, very low-density lipoprotein, and total cholesterol and triglycerides levels) and composition of the HDL subfractions HDL2 and HDL3. SLE patients showed significantly lower contents of Apo A-I, phospholipid, and triglyceride in the HDL3 subfraction (p < 0.05, between-group comparisons) than healthy controls at baseline. The exercise training program did not affect any of the parameters in the SLE-TR group (p > 0.05, within-group comparisons), although there was a trend toward decreased circulating Apo B levels (p = 0.06, ES = -0.3, within-group comparison). In contrast, the same exercise training program was effective in increasing contents of cholesterol, triglyceride, and phospholipid in the HDL2 subfraction in the C-TR group (p = 0.036, ES = 2.06; p = 0.038, ES = 1.77; and p = 0.0021, ES = 2.37, respectively, within-group comparisons), whereas no changes were observed in the composition of the HDL3 subfraction. This study showed that SLE patients have a less effective response to a 12-week exercise training program than healthy individuals, with regard to lipid profile and chemical composition of HDL subfractions. These results reinforce the need for further studies to define the optimal training protocol to improve lipid profile and particularly the HDL composition in these patients (registered at clinicaltrials.gov as NCT01515163).
bookPart Obesidade e metabolismo de lipídios(2015) NAKANDAKARE, Edna Regina; PASSARELLI, Marisa- Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus(2015) MARQUES, T.; PATENTE, T. A.; MONTEIRO, M. B.; CAVALEIRO, A. M.; QUEIROZ, M. S.; NERY, M.; AZEVEDO, M. J. de; CANANI, L. H.; PARISI, M. C.; MOURA-NETO, A.; PASSARELLI, M.; GIANNELLA-NETO, D.; MACHADO, U. F.; CORREA-GIANNELLA, M. L.Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type I diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 +/- 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36,95% CI: 0.16 - 0.80, p = 0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p = 0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient ON and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type I diabetes control.
- Oleic and linoleic fatty acids downregulate Slc2a4/GLUT4 expression via NFKB and SREBP1 in skeletal muscle cells(2015) POLETTO, Ana Claudia; FURUYA, Daniela Tomie; DAVID-SILVA, Aline; EBERSBACH-SILVA, Patricia; SANTOS, Camilo Lellis; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, Marisa; MACHADO, Ubiratan FabresOleic (OA) and linoleic (LA) fatty acids may be important regulators of Slc2a4 gene (GLUT4 protein) in skeletal muscle, thus participating in insulin resistance. We investigated the effect of OA and LA on the Slc2a4/GLUT4 expression in L6 muscle cells; as well as potential transcriptional regulators. OA and LA (50-400 mu M) decreased the Slc2a4/GLUT4 expression in a dose-dependent way (maximum of similar to 50%, P <0.001). OA and LA did not alter the Slc2a4-binding activity of oxysterols-receptor-LXR-alpha and peroxisome-proliferator-activated-receptor-gamma; but decreased the Slc2a4-binding activity of the sterolregulatory-element-binding-protein-1 (SREBP1) enhancer (50%, P <0.001), and increased (similar to 30%, P <0.001) the nuclear proteins binding into the Slc2a4-nuclear-factor-NF-kappa-B-binding site (repressor), and the phosphorylation of the inhibitors of nuclear-factor-kappa-B-kinase alpha/beta (150-300%, P <0.001). In sum, OA and LA are potent inhibitors of the Slc2a4/GLUT4 expression in muscle cells; an effect involving reduced SREBP1 and increased NFKB transcriptional activity. These regulations may participate in the fatty acid-related pathophysiology of insulin resistance.
- Glycated human serum albumin isolated from poorly controlled diabetic patients impairs cholesterol efflux from macrophages: an investigation by mass spectrometry(2015) CASTILHO, Gabriela; SARTORI, Camila H.; MACHADO-LIMA, Adriana; NAKANDAKARE, Edna R.; CORREA-GIANNELLA, Maria Lucia C.; ROVERSO, Marco; PORCU, Simona; LAPOLLA, Annunziata; TRALDI, Pietro; PASSARELLI, MarisaAdvanced glycation end-products impair ABCA-1-mediated cholesterol efflux by eliciting inflammation, the generation of reactive oxygen species and endoplasmatic reticulum (ER) stress. The glycation level of human serum albumin (HSA) from type 1 and type 2 diabetic patients was determined by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and related to possible impairment of ER function and cellular cholesterol efflux. Comparison of the MALDI spectra from healthy and diabetic subjects allowed us to determine an increased HSA mean mass of 1297 Da for type 1 and 890 Da for type 2. These values reflect a mean condensation of at least 8 glucose units and 5 glucose units, respectively. Mouse peritoneal macrophages were treated with HSA from control, type 1 and type 2 diabetic subjects in order to measure the expression of Grp78, Grp94, protein disulfide isomerase (PDI), calreticulin (CRT), and ABCA-1. C-14-cholesterol overloaded-J774 macrophages were treated with HSA from control and diabetic subjects and further incubated with apo A-1 to determine the cholesterol efflux. Combined analyses comprising HSA from type 1 and type 2 diabetic patients were performed in cellular functional assays. In macrophages, PDI expression increased 89% and CRT 3.4 times in comparison to HSA from the control subjects. ABCA-1 protein level and apo A-I-mediated cholesterol efflux were, respectively, 50% and 60% reduced in macrophages exposed to HSA from type 1 and type 2 diabetic patients when compared to that exposed to HSA from control subjects. We provide evidence that the level of glycation that occurs in albumin in vivo damages the ER function related to the impairment in macrophage reverse cholesterol transport, and so contributes to atherosclerosis in diabetes.
- 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(2015) PINTO, Paula Ramos; ROCCO, Debora Dias Ferraretto Moura; OKUDA, Ligia Shimabukuro; MACHADO-LIMA, Adriana; CASTILHO, Gabriela; SILVA, Karolline Santana da; GOMES, Diego Juvenal; PINTO, Raphael de Souza; IBORRA, Rodrigo Tallada; FERREIRA, Guilherme da Silva; NAKANDAKARE, Edna Regina; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria Lucia Cardillo; CATANOZI, Sergio; PASSARELLI, MarisaBackground: Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice. Methods: Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of H-3-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. C-14-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of H-3-cholesteryl oleoyl ether (H-3-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session. Results: Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of H-3-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in H-3-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, C-14-cholestrol efflux and uptake of H-3-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals. Conclusion: Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.
- In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1-Mediated Cholesterol Efflux(2015) MACHADO-LIMA, Adriana; IBORRA, Rodrigo T.; PINTO, Raphael S.; CASTILHO, Gabriela; SARTORI, Camila H.; OLIVEIRA, Erika R.; OKUDA, Ligia S.; NAKANDAKARE, Edna R.; GIANNELLA-NETO, Daniel; MACHADO, Ubiratan F.; CORREA-GIANNELLA, Maria Lucia C.; TRALDI, Pietro; PORCU, Simona; ROVERSO, Marco; LAPOLLA, Annunziata; PASSARELLI, MarisaAdvanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis. AGE-albumin induces oxidative stress, which is linked to a reduction in ABCA-1 and cholesterol efflux. We characterized the glycation level of human serum albumin (HSA) isolated from poorly controlled DM2 (n=11) patients compared with that of control (C, n=12) individuals and determined the mechanism by which DM2-HSA can interfere in macrophage lipid accumulation. The HSA glycation level was analyzed by MALDI/MS. Macrophages were treated for 18h with C- or DM2-HSA to measure the C-14-cholesterol efflux, the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyze gene expression, and the differentially expressed genes were validated by real-time RT-PCR. An increased mean mass was observed in DM2-HSA compared with C-HSA, reflecting the condensation of at least 5 units of glucose. The cholesterol efflux mediated by apo AI, HDL3, and HDL2 was impaired in DM2-HSA-treated cells, which was related to greater intracellular lipid accumulation. DM2-HSA decreased Abcg1 mRNA expression by 26%. Abca1 mRNA was unchanged, although the final ABCA-1 protein content decreased. Compared with C-HAS-treated cells, NADPH oxidase 4 mRNA expression increased in cells after DM2-HSA treatment. Stearoyl-Coenzyme A desaturase 1, janus kinase 2, and low density lipoprotein receptor mRNAs were reduced by DM2-HSA. The level of glycation that occurs in vivo in DM2-HSA-treated cells selectively alters macrophage gene expression, impairing cholesterol efflux and eliciting intracellular lipid accumulation, which contribute to atherogenesis, in individuals with DM2. J. Cell. Physiol. XXXX: XX-XX, 2015. (c) 2015 Wiley Periodicals, Inc. J. Cell. Physiol. 230: 1250-1257, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company