SAYONARA IVANA SANTOS DE ASSIS
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LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
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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.- 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.
- 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.
conferenceObject THE INCREASED ANTIOXIDANT ACTION OF HDL IS INDEPENDENT OF HDL CHOLESTEROL PLASMA LEVELS IN TRIPLE-NEGATIVE BREAST CANCER(2023) CAMPOS, A.; SAWADA, M. I.; SANTANA, M.; IBORRA, R.; ASSIS, S. De; REIS, M.; CARVALHO, J. De; GEBRIM, L. H.; PASSARELLI, M.- The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration(2022) NUNES, Valeria Sutti; SILVA, Eliton Juniro da; FERREIRA, Guilherme da Silva; ASSIS, Sayonara Ivana Santos de; CAZITA, Patricia Miralda; NAKANDAKARE, Edna Regina; ZAGO, Vanessa Helena de Souza; FARIA, Eliana Cotta de; QUINTAO, Eder Carlos RochaNon-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.
- Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors(2023) SAWADA, Maria Isabela Bloise Alves Caldas; SANTANA, Monique de Fatima Mello; REIS, Mozania; ASSIS, Sayonara Ivana Santos de; PEREIRA, Lucas Alves; SANTOS, Danielle Ribeiro; NUNES, Valeria Sutti; CORREA-GIANNELLA, Maria Lucia Cardillo; GEBRIM, Luiz Henrique; PASSARELLI, MarisaThe association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naive BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and C-14-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.
- Plasma advanced glycation end products and soluble receptor for advanced glycation end products as indicators of sterol content in human carotid atherosclerotic plaques(2022) PINTO, Raphael S.; FERREIRA, Guilherme S.; SILVESTRE, Gina Camillo R.; SANTANA, Monique de Fatima M.; NUNES, Valeria S.; LEDESMA, Lucas; PINTO, Paula R.; ASSIS, Sayonara Ivana S. de; MACHADO, Ubiratan F.; SILVA, Erasmo S. da; PASSARELLI, MarisaAdvanced glycation end products (AGEs) are independently related to cardiovascular disease (CVD) and favor cholesterol and oxysterol accumulation in macrophage foam cells. Soluble RAGE (sRAGE) impairs cellular AGE signaling alleviating the deleterious effects of AGE in atherogenesis. The association between plasma AGEs and sRAGE with the content of cholesterol, markers of cholesterol synthesis and absorption, and oxysterols in atherosclerotic plaques was evaluated in subjects undergoing carotid endarterectomy. Plasma and carotid plaques were obtained from symptomatic (n = 23) and asymptomatic subjects (n = 40). Lipids from plaques were extracted and sterols (oxysterols, cholesterol, desmosterol, lathosterol, sitosterol, and campesterol) were determined by using gas chromatography/mass spectrometry. Plasma total AGEs and pentosidine were measured by using fluorimetry and sRAGE by using ELISA. In symptomatic subjects ' atherosclerotic plaques, an increased amount of cholesterol (3x) and oxysterols [7 alpha-hydroxycholesterol (1.4x); 7 beta-hydroxycholesterol (1.2x); 25-hydroxycholesterol (1.3x); 24-hydroxycholesterol (2.7x), and 27-hydroxycholesterol, (1.15x)], with exception to 7 ketocholesterol, were found in comparison to asymptomatic individuals. Plasma total AGEs and pentosidine significantly and positively correlated to sterols accumulated in the atherosclerotic lesion, including cholesterol, desmosterol, campesterol, sitosterol, and oxysterols. On the other hand, sRAGE inversely correlated to total AGEs and pentosidine in plasma, and with major species of oxysterols, cholesterol, and markers of cholesterol synthesis and absorption in the atherosclerotic lesion. In multiple regression analyses, it was observed a significant inverse correlation between sRAGE and 24-hydroxycholesterol and desmosterol, and a positive significant correlation between pentosidine and 24-hydroxycholesterol, 27-hydroxycholesterol, and campesterol. In conclusion, the plasma concentration of AGEs and sRAGE is a tool to predict the accumulation of sterols in atherosclerotic lesions in symptomatic and asymptomatic individuals, helping to prevent and improve the management of acute cardiovascular complications.