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
114 resultados
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- The coronary artery calcium score is linked to plasma cholesterol synthesis and absorption markers: Brazilian Longitudinal Study of Adult Health(2020) NUNES, Valeria Sutti; BENSENOR, Isabela M.; LOTUFO, Paulo A.; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; QUINTAO, Eder Carlos RochaIt is controversial whether atherosclerosis is linked to increased intestinal cholesterol ab-sorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of S ao Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured com-mon carotid artery intima-media thickness (CCA-IMT). Cases with CAC zero had the follow-ing parameters higher than cases with CAC = zero: age, waist circumference (WC), plasma total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and non-high density lipoprotein-cholesterol (non HDL-C). Plasma desmosterol and campesterol, duly corrected for TC, age, body mass index (BMI), waist circumference (WC), hypertension, smoking, and the homeostasis model assessment-insulin resistance (HOMA-IR) correlated with CAC, but not with CCA-IMT. The latter related to increased age, BMI, waist circumference (WC), and systolic blood pressure (SBP). Plasma HDL-C concentrations did not define CAC or CCA-IMT degrees, although in relation to the lower tertile of HDL-C in plasma the higher tertile of HDL-C had lower HOMA-IR and concentration of a cholesterol synthesis marker (desmosterol). Present work indicated that increased cholesterol synthesis and absorption represent primary causes of CAD, but not of the common carotid artery atherosclerosis.
- Dietary sodium restriction alters muscle lipidomics that relates to insulin resistance in mice(2021) PINTO, Paula Ramos; YOSHINAGA, Marcos Y.; BIANCO, Vanessa Del; BOCHI, Ana Paula; FERREIRA, Guilherme S.; PINTO, Isabella F. D.; RODRIGUES, Leticia G.; NAKANDAKARE, Edna R.; OKAMOTO, Maristela M.; MACHADO, Ubiratan F.; MIYAMOTO, Sayuri; CATANOZI, Sergio; PASSARELLI, MarisaA low-sodium (LS) diet has been shown to reduce blood pressure (BP) and the incidence of cardiovascular diseases. However, severe dietary sodium restriction promotes insulin resistance (IR) and dyslipidemia in animal models and humans. Thus, further clarification of the long-term consequences of LS is needed. Here, we investigated the effects of chronic LS on gastrocnemius gene and protein expression and lipidomics and its association with IR and plasma lipids in LDL receptor knockout mice. Three-month-old male mice were fed a normal sodium diet (NS; 0.5% Na; n = 12-19) or LS (0.06% Na; n = 14-20) over 90 days. Body mass (BM), BP, plasma total cholesterol, triacylglycerol (TG), glucose, hematocrit, and IR were evaluated. LS increased BM (9%), plasma TG (51%), blood glucose (19%), and IR (46%) when compared with the NS. RT-qPCR analysis revealed that genes involved in lipid uptake and oxidation were increased by the LS: Fabp3 (106%), Prkaa1 (46%), and Cpt1 (74%). Genes and proteins (assessed by Western blotting) involved in insulin signaling were not changed by the LS. Similarly, lipid species classically involved in muscle IR, such as diacylglycerols and ceramides detected by ultra-high-performance liquid chromatography coupled to mass spectrometry, were also unchanged by LS. Species of phosphatidylcholines (68%), phosphatidylinositol (90%), and free fatty acids (59%) increased while cardiolipins (41%) and acylcarnitines (9%) decreased in gastrocnemius in response to LS and were associated with glucose disposal rate. Together these results suggest that chronic LS alters glycerophospholipid and fatty acids species in gastrocnemius that may contribute to glucose and lipid homeostasis derangements in mice.
- Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice(2018) PINTO, Paula R.; SILVA, Karolline S. da; 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, MarisaAerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session. mRNA was determined by RT-qPCR, protein levels by immunoblot and C-14-cholesterol efflux determined in macrophages. AET did not change body weight, plasma cholesterol, triglycerides, glucose and CETP activity. In macrophages, at time 0 h, a higher expression of genes that encode PPAR gamma, ABCA-1 and a lower expression of MCP-1 and IL-10, was observed in T as compared to S. After 48 h, lower expressions of MCP-1 and PPAR gamma genes were observed in T mice. Increase in ABCA-1, SR-BI and IL-6 and decrease of LOX-1, MCP-1, TNF and IL-10 gene expression was observed in the aorta of T compared to S mice (0 h) and LOX-1 and MCP-1 remained diminished after 48 h. The protein level of MCP-1 and SR-BI in the aortic arch was unchanged in T animals after 48 h as compared to S, but LOX-1 was reduced confirming data of gene expression. The apo A-I and the HDL2 mediated-cholesterol efflux (8 and 24 h) were not different between T and S animals. In the presence of CETP, AET positively influences gene expression in the arterial wall and macrophages of CETP-tg mice contributing to the RCT and prevention of atherosclerosis. These changes were perceptible immediately after the exercise session and were influenced by the presence of CETP although independent of changes in its activity. Reductions in gene and protein expression of LOX-1 were parallel and reflect the ability of exercise training in reducing the uptake of modified LDL by the arterial wall macrophages.
conferenceObject INCREASED EXPRESSION OF MIR-223-3P AND MIR-375-3P IN HDL TOGETHER WITH A HIGH ANTI-INFLAMMATORY CAPACITY OF HDL IN BREAST CANCER(2023) SANTANA, M.; SAWADA, M. I.; SANTOS, A.; PEREIRA, L.; GEBRIM, L. H.; SORIANO, F.; REIS, M.; HIRATA, A. H. D. L. H.; CAMACHO, C.; PASSARELLI, M.- Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects(2013) LEANCA, Camila C.; NUNES, Valeria S.; PANZOLDO, Natalia B.; ZAGO, Vanessa S.; PARRA, Eliane S.; CAZITA, Patricia M.; JAUHIAINEN, Matti; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; FARIA, Eliana C. de; QUINTAO, Eder C. R.Background: We have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects. Methods: We have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-1HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption. Results: In the high-HDL-C group, we found lower plasma concentrations of triglycerides, alanine aminotransferase, insulin, HOMA-IR index, activities of LCAT and HL compared with the low HDL-C group; additionally, we found higher activity of LPL and pre-beta-1HDL concentration in the high-HDL-C group. There were no differences in the plasma CETP and PLTP activities. Conclusions: These findings indicate that in healthy hyperalphalipoproteinemia subjects, several parameters that control the metabolism of plasma cholesterol and lipoproteins are related to a higher degree of insulin sensitivity.
conferenceObject The role of beta 1 adrenergic receptor in Non-Alcoholic Fat Liver Disease development(2013) FERNANDES, Gustavo Werpel; MARCELINO, Cicera Pimenta; BRUM, Patricia Chakur; PASSARELLI, Marisa; BOCCO, Barbara Miranda Leite da Costa; RIBEIRO, Miriam OliveiraNon-Alcoholic Fat Liver Disease (NAFLD) is characterized by the development of macrovesicular steatosis in the absence of significant consumption of alcohol, which can progress to nonalcoholic steato-hepatitis (NASH). Knockout mice for the β1 adrenergic receptor (β1KO) are obese when placed on high fat diet (HFD) and develop NASH with severe steatosis and fibrosis. The aim of this study was to determine if β1 adrenergic receptors have a direct role in NASH development or if this abnormality is due to the severe obesity observed in these mice. For that we analyzed genes related to lipid metabolism in the liver of obese β1KO. Fatty acids, triglycerides and cholesterol synthesis were increased in β1KO HFD (ChREBP: 5.55±0.2 vs. 2.28±0.04 WT, p<0.05; SREBP1c: 2.52±0.4 vs. 1.32±0.02 WT, p<0.05; DGAT2: 2±0.3 vs. 1.3±0.1 WT, p<0.05; SREBP2: 3.22±0.5 vs. 0.67±0.06 WT, p<0.05) resulting in hepatic triglycerides accumulation whereas hepatic secretion of lipoproteins were decreased (MTTP: 0.32±0.01 vs. 0.6±0.03 WT, p<0.05). These data showed an imbalance in lipoproteins synthesis and export, resulting in NASH. In conclusion, β1 adrenergic receptor has a direct influence on expression of genes related to lipid metabolism, and its absence leads to NASH when mice are treated with HFD.- Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users(2019) SOUZA, Francis Ribeiro de; SANTOS, Marcelo Rodrigues Dos; PORELLO, Rafael Armani; FONSECA, Guilherme Wesley Peixoto da; SAYEGH, Ana Luiza Carrari; LIMA, Thais Pinheiro; FERREIRA, Fabiana Dias; OLIVEIRA, Tiago Franco de; YONAMINE, Mauricio; TAKAYAMA, Liliam; PEREIRA, Rosa Maria Rodrigues; NEGRAO, Carlos Eduardo; PASSARELLI, Marisa; ROCHITTE, Carlos Eduardo; ALVES, Maria Janieire de Nazare NunesBackground and aims: Anabolic androgenic steroids (AAS) have been associated with coronary artery disease (CAD). AAS abuse leads to a remarkable decrease in high-density lipoprotein (HDL) plasma concentration, which could be a key factor in the atherosclerotic process. Moreover, not only the concentration of HDL, but also its functionality, plays a pivotal role in CAD. We tested the functionality of HDL by cholesterol efflux and antioxidant capacity. We also evaluated the prevalence of CAD in AAS users. Methods: Twenty strength-trained AAS users (AASU) age 29 +/- 5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this cross-sectional study. Functionality of HDL was evaluated by C-14-cholesterol efflux and the ability of HDL in inhibiting LDL oxidation. Coronary artery was evaluated with coronary computed tomography angiography. Results: Cholesterol efflux was lower in AASU compared with AASNU and SC (20 vs. 23 vs. 24%, respectively, p < 0.001). However, the lag time for LDL oxidation was higher in AASU compared with AASNU and SC (41 vs 13 vs 11 min, respectively, p < 0.001). We found at least 2 coronary arteries with plaques in 25% of AASU. None of the AASNU and SC had plaques. The time of AAS use was negatively associated with cholesterol efflux. Conclusions: This study indicates that AAS abuse impairs the cholesterol efflux mediated by HDL. Long-term AAS use seems to be correlated with lower cholesterol efflux and early subclinical CAD in this population.
- Postmortem Brains from Subjects with Diabetes Mellitus Display Reduced GLUT4 Expression and Soma Area in Hippocampal Neurons: Potential Involvement of Inflammation(2023) YONAMINE, Caio Yogi; PASSARELLI, Marisa; SUEMOTO, Claudia Kimie; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; ALVES, Venancio Avancini Ferreira; MARIE, Suely Kazue Nagahashi; CORREA-GIANNELLA, Maria Lucia; BRITTO, Luiz Roberto; MACHADO, Ubiratan FabresDiabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed neuronal glucose supply plays a key role, which in hippocampal neurons is controlled by the insulin-sensitive glucose transporter type 4 (GLUT4). We investigated the expression of GLUT4, nuclear factor NF-kappa B subunit p65 [NFKB (p65)], carboxymethyllysine and synapsin1 (immunohistochemistry), and soma area in human postmortem hippocampal samples from control, obese, and obese+DM subjects (41 subjects). Moreover, in human SH-SY5Y neurons, tumor necrosis factor (TNF) and glycated albumin (GA) effects were investigated in GLUT4, synapsin-1 (SYN1), tyrosine hydroxylase (TH), synaptophysin (SYP) proteins, and respective genes; NFKB binding activity in the SLC2A4 promoter; effects of increased histone acetylation grade by histone deacetylase 3 (HDAC3) inhibition. Hippocampal neurons (CA4 area) of obese+DM subjects displayed reduced GLUT4 expression and neuronal soma area, associated with increased expression of NFKB (p65). Challenges with TNF and GA decreased the SLC2A4/GLUT4 expression in SH-SY5Y neurons. TNF decreased SYN1, TH, and SYP mRNAs and respective proteins, and increased NFKB binding activity in the SLC2A4 promoter. Inhibition of HDAC3 increased the SLC2A4 expression and the total neuronal content of CRE-binding proteins (CREB/ICER), and also counterbalanced the repressor effect of TNF upon these parameters. This study revealed reduced postmortem human hippocampal GLUT4 content and neuronal soma area accompanied by increased proinflammatory activity in the brains of DM subjects. In isolated human neurons, inflammatory activation by TNF reduced not only the SLC2A4/GLUT4 expression but also the expression of some genes related to neuronal function (SYN1, TH, SYP). These effects may be related to epigenetic regulations (H3Kac and H4Kac status) since they can be counterbalanced by inhibiting HDAC3. These results uncover the improvement in GLUT4 expression and/or the inhibition of HDAC3 as promising therapeutic targets to fight DM-related neurodegeneration.
conferenceObject N-acetylcystein Reduces Lipid Peroxidation and Advanced Glycation Related to Prevention of Macrophage Endoplasmic Reticulum Stress Induced by Albumin Isolated from Rats With Chronic Kidney Disease(2014) MACHADO, Juliana T.; IBORRA, Rodrigo T.; FUSCO, Fernanda B.; CASTILHO, Gabriela; PINTO, Raphael S.; MACHADO-LIMA, Adriana; NAKANDAKARE, Edna R.; SHIMIZU, Maria Heloisa M.; SEGURO, Antonio Carlos; CATANOZI, Sergio; PASSARELLI, MarisaconferenceObject CHRONIC ADMINISTRATION OF ALBUMIN MODIFIED BY ADVANCED GLYCATION (AGE) INDUCES EXPRESSION OF PRO-FIBROTIC, PRO-APOPTOTIC AND RENIN-ANGIOTENSIN SYSTEM GENES ON RENAL TISSUE(2016) THIEME, Karina; FABRE, Nelly Takashima; SILVA, Karolline Santana da; CATANOZI, Sergio; MONTEIRO, Maria Beatriz; MACHADO, Ubiratan Fabres; PASSARELLI, Marisa; CORREA-GIANNELLA, Maria Lucia Cardillo