MONIQUE DE FATIMA MELLO SANTANA
Projetos de Pesquisa
Unidades Organizacionais
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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- 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.
- 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.
- 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.
- Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer(2023) SANTANA, Monique de Fatima Mello; SAWADA, Maria Isabela Bloise Alves Caldas; SANTOS, Aritania Sousa; REIS, Mozania; XAVIER, Jacira; CORREA-GIANNELLA, Maria Lucia; HIRATA, Andrea Harumy de Lima; GEBRIM, Luiz Henrique; SORIANO, Francisco Garcia; CAMACHO, Cleber Pinto; PASSARELLI, MarisaThe expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naive of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.