MONIQUE DE FATIMA MELLO SANTANA
Projetos de Pesquisa
Unidades Organizacionais
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
19 resultados
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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.conferenceObject IMPAIRED HDL-MEDIATED CELL CHOLESTEROL REMOVAL IN ADVANCED BREAST CANCER(2023) SAWADA, M. I.; SANTANA, M.; REIS, M.; ASSIS, S. De; PEREIRA, L.; SANTOS, D.; NUNES, V.; CORREA-GIANNELLA, M. L.; GEBRIM, L. H.; PASSARELLI, M.conferenceObject PLASMA ADVANCED GLYCATION END PRODUCTS POSITIVELY CORRELATES TO OXYSTEROLS LEVELS IN CAROTID ATHEROSCLEROTIC PLAQUES(2020) PINTO, R. S.; FERREIRA, G. S.; SILVESTRE, G. C. R.; SANTANA, M. F. M.; LEDESMA, L.; PINTO, P. R.; MARCELINO, G. A.; SILVA, E. S. Da; PASSARELLI, M.- Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case-control study(2023) TOYOSHIMA, Marcos Tadashi K.; SANTANA, Monique F. M.; SILVA, Amanda R. M.; MELLO, Gabriela B. B.; SANTOS-BEZERRA, Daniele P. P.; GOES, Marisa F. S.; BOSCO, Adriana A. A.; CARAMELLI, Bruno; RONSEIN, Graziella E. E.; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, MarisaBackgroundSubclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality.MethodsA total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages.ResultsAmong 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use.ConclusionHDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.
- Novel Role of CETP in Macrophages: Reduction of Mitochondrial Oxidants Production and Modulation of Cell Immune-Metabolic Profile(2022) DORIGHELLO, Gabriel G.; ASSIS, Leandro H. P.; RENTZ, Thiago; MORARI, Joseane; SANTANA, Monique F. M.; PASSARELLI, Marisa; RIDGWAY, Neale D.; VERCESI, Anibal E.; OLIVEIRA, Helena C. F.Plasma cholesteryl ester transfer protein (CETP) activity diminishes HDL-cholesterol levels and thus may increase atherosclerosis risk. Experimental evidence suggests CETP may also exhibit anti-inflammatory properties, but local tissue-specific functions of CETP have not yet been clarified. Since oxidative stress and inflammation are major features of atherogenesis, we investigated whether CETP modulates macrophage oxidant production, inflammatory and metabolic profiles. Comparing macrophages from CETP-expressing transgenic mice and non-expressing littermates, we observed that CETP expression reduced mitochondrial superoxide anion production and H2O2 release, increased maximal mitochondrial respiration rates, and induced elongation of the mitochondrial network and expression of fusion-related genes (mitofusin-2 and OPA1). The expression of pro-inflammatory genes and phagocytic activity were diminished in CETP-expressing macrophages. In addition, CETP-expressing macrophages had less unesterified cholesterol under basal conditions and after exposure to oxidized LDL, as well as increased HDL-mediated cholesterol efflux. CETP knockdown in human THP1 cells increased unesterified cholesterol and abolished the effects on mitofusin-2 and TNF alpha. In summary, the expression of CETP in macrophages modulates mitochondrial structure and function to promote an intracellular antioxidant state and oxidative metabolism, attenuation of pro-inflammatory gene expression, reduced cholesterol accumulation, and phagocytosis. These localized functions of CETP may be relevant for the prevention of atherosclerosis and other inflammatory diseases.
- The Prolonged Activation of the p65 Subunit of the NF-Kappa-B Nuclear Factor Sustains the Persistent Effect of Advanced Glycation End Products on Inflammatory Sensitization in Macrophages(2024) ASSIS, Sayonara Ivana Santos de; AMENDOLA, Leonardo Szalo; OKAMOTO, Maristela Mitiko; FERREIRA, Guilherme da Silva; IBORRA, Rodrigo Tallada; SANTOS, Danielle Ribeiro; SANTANA, Monique de Fatima Mello; SANTANA, Kelly Gomes; CORREA-GIANNELLA, Maria Lucia; BARBEIRO, Denise Frediani; SORIANO, Francisco Garcia; MACHADO, Ubiratan Fabres; PASSARELLI, MarisaAdvanced glycation end products (AGEs) prime macrophages for lipopolysaccharide (LPS)-induced inflammation. We investigated the persistence of cellular AGE-sensitization to LPS, considering the nuclear content of p50 and p65 nuclear factor kappa B (NFKB) subunits and the expression of inflammatory genes. Macrophages treated with control (C) or AGE-albumin were rested for varying intervals in medium alone before being incubated with LPS. Comparisons were made using one-way ANOVA or Student t-test (n = 6). AGE-albumin primed macrophages for increased responsiveness to LPS, resulting in elevated levels of TNF, IL-6, and IL-1beta (1.5%, 9.4%, and 5.6%, respectively), compared to C-albumin. TNF, IL-6, and IL-1 beta secretion persisted for up to 24 h even after the removal of AGE-albumin (area under the curve greater by 1.6, 16, and 5.2 times, respectively). The expressions of Il6 and RelA were higher 8 h after albumin removal, and Il6 and Abca1 were higher 24 h after albumin removal. The nuclear content of p50 remained similar, but p65 showed a sustained increase (2.9 times) for up to 24 h in AGE-albumin-treated cells. The prolonged activation of the p65 subunit of NFKB contributes to the persistent effect of AGEs on macrophage inflammatory priming, which could be targeted for therapies to prevent complications based on the AGE-RAGE-NFKB axis.
- Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease(2021) LIRA, Aecio Lopes de Araujo; SANTANA, Monique de Fatima Mello; PINTO, Raphael de Souza; MINANNI, Carlos Andre; IBORRA, Rodrigo Tallada; LIMA, Adriana Machado Saldiba de; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, Marisa; QUEIROZ, Marcia SilvaBackground and aims: Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. Material and methods: 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry. In the isolated albumins, we quantified CBL (ELISA) and total AGE and pentosidine by fluorescence. Macrophages were treated with albumin isolated, and 14C-Cholesterol efflux mediated by HDL2 or HDL3 was measured. Kruskal-Wallis test, Jonckheere-Terpstra test and Brunner's posttest were used for comparisons among groups. Results: Determination of CML, HCit, CBL in plasma, as total AGE and pentosidine in albumins, did not differ between groups; however, CBL in the isolated albumins was higher in the more advanced stages of CKD (p = 0.0414). There was reduction in the 14C-cholesterol efflux after treatment for 18 h with albumin isolated from patients with eGFR<60 mL/min/1.73m2 compared with control group mediated by HDL2 (p = 0.0288) and HDL3 (p < 0.0001), as well as when compared with eGFR >= 60 mL/min/1.73m2 per HDL2 (p = 0.0001) and HDL3 (p < 0.0001). Treatment for 48 h showed that eGFR<15 mL/min/1.73m2 had a lower percentage of 14Ccholesterol efflux mediated by HDL2 compared to control and other CKD groups (p = 0.0274). Conclusions: Albumins isolated from individuals with T2DM and eGFR<60 mL/min/1.73m2 suffer greater carbamoylation, and they impair the cholesterol efflux mediated by HDL2 and HDL3. In turn, this could promote lipids accumulation in macrophages and disorders in reverse cholesterol transport.
- Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis(2020) SANTANA, Monique F. M.; LIRA, Aecio L. A.; PINTO, Raphael S.; MINANNI, Carlos A.; SILVA, Amanda R. M.; SAWADA, Maria I. B. A. C.; NAKANDAKARE, Edna R.; CORREA-GIANNELLA, Maria L. C.; QUEIROZ, Marcia S.; RONSEIN, Graziella E.; PASSARELLI, MarisaBackground and aims Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods Individuals with DKD were divided into eGFR> 60 mL/min/1.73 m(2)plus AER stages A1 and A2 (n = 10) and eGFR< 60 plus A3 (n = 25) and matched by age with control subjects (eGFR> 60;n = 8). Results Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR< 60 + A3 group than in the controls: apolipoprotein D (apoD) and apoA-IV. HDL from the eGFR< 60 + A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove(14)C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR< 60 + A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.
conferenceObject IMPROVEMENT OF GLYCEMIC CONTROL RESTORES ABCA-1 IN MACROPHAGES INCUBATED WITH ALBUMIN ISOLATED FROM DIABETIC SUBJECTS(2018) IBORRA, R. Tallada; MACHADO-LIMA, A.; OKUDA, L. S.; MINANNI, C.; MELLO, M.; NAKANDAKARE, E. R.; MACHADO, U. F.; CORREA-GIANELLA, M. L. C.; PASSARELLI, M.- The increased antioxidant action of HDL is independent of HDL cholesterol plasma levels in triple-negative breast cancer(2023) CAMPOS, Amarilis de Lima; SAWADA, Maria Isabela Bloise Alves Caldas; SANTANA, Monique Fatima de Mello; IBORRA, Rodrigo Tallada; ASSIS, Sayonara Ivana Santos de; REIS, Mozania; CARVALHO, Jacira Xavier de; GEBRIM, Luiz Henrique; PASSARELLI, MarisaIntroductionThe association between high-density lipoprotein cholesterol (HDLc) with the incidence and progression of breast cancer (BC) is controversial. HDL removes excess cholesterol from cells and acts as an antioxidant and anti-inflammatory. BC is a heterogeneous disease, and its molecular classification is important in the prediction of clinical and therapeutic evolution. Triple-negative breast cancer (TNBC) presents higher malignancy, lower therapeutic response, and survival rate. In the present investigation, the composition and antioxidant activity of isolated HDL was assessed in women with TNBC compared to controls. MethodsTwenty-seven women with a recent diagnosis of TNBC, without prior treatment, and 27 healthy women (control group) paired by age and body mass index (BMI) were included in the study. HDL and low-density lipoprotein (LDL) were isolated from plasma by discontinuous density gradient ultracentrifugation. Plasma lipid profile and HDL composition (total cholesterol, TC; triglycerides, TG; HDLc; phospholipids, PL) were determined by enzymatic colorimetric methods. ApoB and apo A-I were quantified by immunoturbidimetry. The antioxidant activity of HDL was determined by measuring the lag time phase for LDL oxidation and the maximal rate of conjugated dienes formation in LDL incubated with copper sulfate solution. The absorbance (234 nm) was monitored at 37 degrees C, for 4 h, at 3 min intervals. ResultsThe control group was similar to the TNBC concerning menopausal status, concentrations, and ratios of plasma lipids. The composition of the HDL particle in TC, TG, PL, and apo A-I was also similar between the groups. The ability of HDL to retard LDL oxidation was 22% greater in the TNBC group as compared to the control and positively correlated with apoA-I in HDL. Moreover, the antioxidant activity of HDL was greater in the advanced stages of TNBC (stages III and IV) compared to the control group. The maximum rate of formation of conjugated dienes was similar between groups and the clinical stages of the disease. DiscussionThe results highlight the role of HDL as an antioxidant defense in TNBC independently of HDLc plasma levels. The improved antioxidant activity of HDL, reflected by retardation in LDL oxidation, could contribute to limiting oxidative and inflammatory stress in advanced stages of TNBC.