BRUNA MIRANDA DE OLIVEIRA SILVA

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  • article 1 Citação(ões) na Scopus
  • article 0 Citação(ões) na Scopus
    Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE)
    (2023) ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; GUIDO, Maria Carolina; CARVALHO, Priscila Oliveira; TAVONI, Thauany Martins; LOPES, Natalia Menezes; SILVA, Bruna Miranda de Oliveira; JENSEN, Leonardo; STOLF, Noedir Antonio Groppo; MARANHA, Raul Cavalcante
    Atherosclerosis is a cell-proliferative, chronic inflammatory process. The aim was to investigate whether lipid core nanoparticles (LDE) carrying the anti-cancer agent daunorubicin could have anti-atherosclerotic effects. LDE is taken-up by cellular lipoprotein receptors and is capable of concentrating incorporated drugs in inflammed tissues. New Zealand male rabbits were fed 1% cholesterol diet for 8 weeks. Then, animals were treated with LDE-daunorubicin (6 mg/kg/week, IV, n = 9) or with LDE only (n = 7). Atherosclerotic lesions in LDE-daunorubicin group were 50% smaller than in LDE group. In LDE-daunorubicin, protein expressions of the pro-inflammatory markers CD68, TNF-alpha IL-6 and gene expression MCP-1 were lower than in LDE. Gene expression of IL-1 beta, IL-18 and IL-10 were similar. Protein expressions of VEGF and of pro-apoptotic caspase 3, caspase 9 and BAX, and both protein and gene expressions of VCAM-1 were all lower in LDE-daunorubicin. Gene expression of MMP-12 and protein expression of MMP-2 were lower in LDE-daunorubicin, but MMP-9 was not different. Daunorubicin is known as cardiotoxic, but at echocardiography, LDE-daunorubicin had no differences in arch aorta diameters, systolic and diastolic function and in cardiac hypertrophy compared to LDE group. LDEdaunorubicin was capable of reducing atherosclerotic lesions by different mechanisms without observable toxicities.
  • conferenceObject
    LIPID TRANSFERS TO HDL ARE DIMINISHED IN WOMEN WITH OVERT HYPOTHYROIDISM AFTER TOTAL THYROIDECTOMY
    (2018) SIGAL, A.; TAVONI, T. M.; FREITAS, F. R.; SILVA, B. M. O.; BRANDAO, L. G.; MARANHAO, R. C.
  • article 22 Citação(ões) na Scopus
    Effects of Short-Term Hypothyroidism on the Lipid Transfer to High-Density Lipoprotein and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer
    (2019) SIGAL, Gilbert A.; TAVONI, Thauany M.; SILVA, Bruna M. O.; KALIL FILHO, Roberto; BRANDAO, Lenine G.; MARANHAO, Raul C.
    Background: Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. Methods: Eighteen women (age 44 +/- 11 years; body mass index 27.9 +/- 5.2 kg/m(2)) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. Results: Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 +/- 35 vs. 167 +/- 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 +/- 8 vs. 46 +/- 10 mg/dL; p = 0.0025), non-HDL-C (149 +/- 38 vs. 201 +/- 46 mg/dL; p < 0.0001), unesterified cholesterol (53 +/- 10 vs. 70 +/- 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 +/- 0.19 vs. 1.44 +/- 0.22 g/L; p < 0.04), and apo B (0.97 +/- 0.25 vs. 1.31 +/- 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 +/- 0.03 vs. 0.11 +/- 0.02; p < 0.0001), triglycerides (0.11 +/- 0.02 vs. 0.09 +/- 0.02; p < 0.0001), phospholipids (0.44 +/- 0.09 vs. 0.40 +/- 0.07; p = 0.0205), and esterified cholesterol (0.14 +/- 0.03 vs. 0.13 +/- 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. Conclusions: In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.
  • article 8 Citação(ões) na Scopus
    Lipid core nanoparticles resembling low-density lipoprotein and regression of atherosclerotic lesions: effects of particle size
    (2018) FREITAS, S. C. M. P.; TAVARES, E. R.; SILVA, B. M. O.; MENEGHINI, B. C.; KALIL-FILHO, R.; MARANHAO, R. C.
    Particles are usually polydispersed and size is an important feature for lipid-based drug delivery systems in order to optimize cell-particle interactions as to pharmacologic action and toxicity. Lipid nanoparticles (LDE) with composition similar to that of low-density lipoprotein carrying paclitaxel were shown to markedly reduce atherosclerosis lesions induced in rabbits by cholesterol feeding. The aim of this study was to test whether two LDE fractions, one with small (20-60 nm) and the other with large (60-100 nm) particles, had different actions on the atherosclerotic lesions. The two LDE-paclitaxel fractions, prepared by microfluidization, were separated by density gradient ultracentrifugation and injected (4 mg/body weight, intravenously once a week) into two groups of rabbits previously fed cholesterol for 4 weeks. A group of cholesterol-fed animals injected with saline solution was used as control to assess lesion reduction with treatment. After the treatment period, the animals were euthanized for analysis. After treatment, both the small and large nanoparticle preparations of LDE-paclitaxel had equally strong anti-atherosclerosis action. Both reduced lesion extension in the aorta by roughly 50%, decreased the intima width by 75% and the macrophage presence in the intima by 50%. The two preparations also showed similar toxicity profile. In conclusion, within the 20-100 nm range, size is apparently not an important feature regarding the LDE nanoparticle system and perhaps other solid lipid-based systems.
  • conferenceObject
    Daunorubicin associated to lipid core nanoparticles reduces atherosclerotic lesions, inflammation and cardiotoxicity in atherosclerosis rabbit model
    (2020) I, C. Albuquerque; TAVARES, E. R.; GUIDO, M. G.; LOPES, N. M.; V, R. Baroni; JENSEN, L.; SILVA, B. M. O.; KALIL-FILHO, R.; TAVONI, T. M.; MARANHAO, R. C.
  • conferenceObject
    PLASMA LIPIDS AND LIPID TRANSFER TO HDL IN LONG-TERM BEDRIDDEN AND IN SEDENTARY SUBJECTS
    (2017) MARANHAO, Raul Cavalcante; OLIVEIRA, Wilson Camargo De; TAVONI, Thauany Martins; FREITAS, Fatima Rodrigues; SILVA, Bruna Miranda; KALIL-FILHO, Roberto
  • article 2 Citação(ões) na Scopus
    Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers
    (2017) OLIVEIRA, Wilson Pascoalino Camargo de; TAVONI, Thauany Martins; FREITAS, Fatima Rodrigues; SILVA, Bruna Miranda Oliveira; MARANHAO, Raul Cavalcante
    Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (> 90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 +/- 36 vs 160 +/- 43, p = 0.005), LDL (124 +/- 3 vs 96 +/- 33 p = 0.003) and HDL-cholesterol (45 +/- 10 vs 36 +/- 13, p = 0.008), apolipoprotein A-I (134 +/- 20 vs 111 +/- 24, p = 0.001) and oxidized LDL (53 +/- 13 vs 43 +/- 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1 beta, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.
  • article 13 Citação(ões) na Scopus
    Cholesteryl ester transfer protein (CETP), HDL capacity of receiving cholesterol and status of inflammatory cytokines in patients with severe heart failure
    (2018) MARTINELLI, Ana Elisa M.; MARANHAO, Raul C.; CARVALHO, Priscila O.; FREITAS, Fatima R.; SILVA, Bruna M. O.; CURIATI, Milena N. C.; KALIL FILHO, Roberto; PEREIRA-BARRETTO, Antonio Carlos
    BackgroundHeart failure (HF) courses with chronic inflammatory process and alterations in lipid metabolism may aggravate the disease. The aim was to test whether the severity of HF, using brain natriuretic peptide (BNP) as a marker, is associated with alterations in functional aspects of HDL, such as lipid transfer, cholesterol ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) concentration.MethodsTwenty-five HF patients in NYHA class I/II and 23 in class III/IV were enrolled. Plasma lipids, apolipoproteins, CETP, LCAT, oxidized-LDL (oxLDL) and paraoxonase-1 (PON-1) activity were determined. Lipid transfer from a donor artificial nanoparticle to HDL was measured by in vitro assay.ResultsTotal cholesterol (p=0.049), LDL-C (p=0.023), non-HDL-C (p=0.029) and CETP, that promotes lipid transfer among lipoproteins (p=0.013), were lower in III/IV than in I/II group. Triglycerides, HDL-C, apo A-I, apo B, oxLDL, LCAT, enzyme that catalyzes serum cholesterol esterification, PON-1 activity, and in vitro transfers of cholesterol, triglycerides and phospholipids to HDL, important steps in HDL metabolism, were equal. IL-8 was higher in III/IV (p=0.025), but TNF, IL-1, IL-6 and MCP-1 were equal. BNP was negatively correlated with CETP (r=-0.294; p=0.042) and positively correlated with IL-8 (r=0.299; p=0.039).ConclusionsOur results disclosed the relationship between CETP levels and HF severity, by comparing two HF groups and by correlation analysis. Lower CETP levels may be a marker of HF aggravation and possibly of worse prognosis. Practical applications of this initial finding, as the issue whether CETP could be protective against HF aggravation, should be explored in larger experimental and clinical studies.
  • article 7 Citação(ões) na Scopus
    Subclinical Hyperthyroidism: Status of the Cholesterol Transfers to HDL and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer
    (2020) SIGAL, Gilbert A.; TAVONI, Thauany M.; SILVA, Bruna M. O.; KHALIL-FILHO, Roberto; BRANDAO, Lenine G.; BARACAT, Edmund C.; MARANHAO, Raul C.
    Purpose: Lipid metabolism has been poorly explored in subclinical hyperthyroidism. The aim was to examine the effects of exogenous subclinical hyperthyroidism in women under levothyroxine treatment upon plasma lipids and aspects of HDL metabolism. Methodology: Ten women were studied in euthyroidism and again in exogenous subclinical hyperthyroidism. Thyroid function tests and plasma lipids were studied. Results: HDL-cholesterol (increased 21.6%, p = 0.0004), unesterified cholesterol (increased 12.3%, p = 0.04) and Lp(a) (increased 33,3%, P = 0.02) plasma concentrations were higher in subclinical hyperthyroidism compared to euthyroidism, but total cholesterol, LDL, non-HDL cholesterol, triglycerides, apo A-I, apo B were unchanged. PON1 activity (decreased 75%, p = 0.0006) was lower in subclinical hyperthyroidism. There were no changes in HDL particle size, CETP and LCAT concentrations. The in vitro assay that estimates the lipid transfers to HDL showed that esterified cholesterol (increased 7.1%, p = 0.03), unesterified cholesterol (increased 7.8%, p = 0.02) and triglycerides (increased 6.8%, p = 0.006) transfers were higher in subclinical hyperthyroidism. There were no changes in phospholipid transfers to HDL in subclinical hyperthyroidism. Conclusions: Several alterations in the plasma lipid metabolism were observed in the subclinical hyperthyroidism state that highlight the importance of this aspect in the follow-up of those patients. The increase in HDL-C and in the transfer of unesterified and esterified cholesterol to HDL, an important anti-atherogenic HDL function are consistently protective for cardiovascular health. The increase in Lp(a) and the decrease in PON-1 activity that are important risk factors were documented here in subclinical hyperthyroidism and these results should be confirmed in larger studies due to great data variation but should not be neglected in the follow-up of those patients.