RAUL CAVALCANTE MARANHAO
Projetos de Pesquisa
Unidades Organizacionais
FBC, FCF - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
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- Response to Dullaart re: ""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.
- Nanotechnology for the treatment of deep endometriosis: uptake of lipid core nanoparticles by LDL receptors in endometriotic foci(2019) BEDIN, Alessandra; MARANHAO, Raul C.; TAVARES, Elaine R.; CARVALHO, Priscila O.; BARACAT, Edmund C.; PODGAEC, SergioOBJECTIVE: Rapidly dividing cells in multiple types of cancer and inflammatory diseases undergo high low density lipoprotein (LDL) uptake for membrane synthesis, and coupling an LDL-like nanoemulsion, containing lipid nanoparticles (LDE) to a chemotherapeutic agent efficiently targets these cells without significant systemic effects. This was a prospective exploratory study that evaluated the uptake of a radioactively labeled LDE emulsion by receptors of endometriotic foci and the capacity of the LDE for cellular internalization. METHODS: The lipid profile of each patient was determined before surgery, and labeled LDE were injected into fourteen patients with intestinal or nonintestinal endometriosis. The radioactivity of each tissue sample (intestinal endometriosis, nonintestinal endometriosis, healthy peritoneum, or topical endometrium) was measured. RESULTS: The group with intestinal endometriosis presented higher levels of plasma LDL but lower LDE uptake by foci than the nonintestinal group, suggesting less cell division and more fibrosis. The uptake of LDE was highest in the topical endometrium, followed by the healthy peritoneum, and lowest in the endometriotic lesion. Since the endometriotic foci showed significant LDE uptake, there was likely increased consumption of LDL by these cells, similar to cells in cancers and inflammatory diseases. Plasma cholesterol levels had no influence on LDE uptake, which showed that the direct delivery of the nanoemulsion to target tissues was independent of serum lipoproteins. There were no significant differences in the parameters (p > 0.01) because of the small sample size, but the findings were similar to those of previous studies. CONCLUSION: Nanotechnology is a promising therapeutic option for surgery and hormonal blockage for deep endometriosis, with a lower complication rate and no systemic side effects.
- Aerobic Training in Young Men Increases the Transfer of Cholesterol to High Density Lipoprotein In Vitro: Impact of High Density Lipoprotein Size(2019) SILVA, Jeferson L. da; MARANHAO, Raul C.; SILVA, Michelle S. M.; DIAS, Rodrigo G.; FREITAS, Fatima R.; BOLANI, Wladimir; LEMOS JUNIOR, Jose R.; ALVES, Cleber R.; OLIVEIRA, Patricia A.; ALVES, Guilherme B.; OLIVEIRA, Edilamar M.; NEGRAO, Carlos Eduardo; KRIEGER, Jose Eduardo; PEREIRA, Alexandre C.; SILVA, Gisele A.; SOUZA, Jose P.; VINAGRE, Carmen G. C.Exercise training not only improves the plasma lipid profile but also reduces risk of developing coronary heart disease. We investigate whether plasma lipids and high density lipoprotein (HDL) metabolism are affected by aerobic training and whether the high-density lipoprotein cholesterol (HDL-C) levels at baseline influence exercise-induced changes in HDL. Seventy-one male sedentary volunteers were evaluated and allocated in two subgroups, according to the HLD-C levels (< or >40 mg/dL). Participants underwent an 18-week aerobic training period. Blood was sampled before and after training for biochemical analysis. Plasma lipids, apolipoproteins, HDL diameter, and VO2 peak were determined. Lipid transfers to HDL were determined in vitro by incubating plasma samples with a donor lipid artificial nanoemulsion. After the 18-week period of aerobic training, the VO2 peak increased, while the mean body mass index (BMI) decreased. HDL-C concentration was higher after the training period, but low-density lipoprotein cholesterol (LDL-C) and non-HDL-C did not change. The transfer of esterified cholesterol and phospholipids was greater after exercise training, but the triacylglycerol and unesterified cholesterol transfers were unchanged. The HDL particle diameter increased after aerobic training in all participants. When the participants were separated in low-HDL and normal-HDL groups, the postaerobic exercise increment in HDL-C was higher in the low-HDL group, while the transfer of esterified cholesterol was lower. In conclusion, aerobic exercise training increases the lipid transfers to HDL, as measured by an in vitro method, which possibly contributes to the classical elevation of the HDL-C associated with training.
conferenceObject Methotrexate reduces cardiac remodeling and improves left ventricle function in rats with Takotsubo cardiomyopathy(2019) GUIDO, M. C.; LOPES, N. M.; TAVARES, E. R.; BISPO, D. L.; MELO, M. D. Tavares De; SALEMI, V. M. C.; MARANHAO, R. C.bookPart Metabolismo de lípides plasmáticos e exercicio fisico(2019) NUNES, Ana Paula de Oliveira Barbosa; VINAGRE, Carmen Guilherme Christiano de Matos; MARANHãO, Raul Cavalcante- 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.
- Lipid transfer to high-density lipoproteins in coronary artery disease patients with and without previous cerebrovascular ischemic events(2019) BARBOSA, Carlos J. D. G.; MARANHAO, Raul C.; BARREIROS, Renata S.; FREITAS, Fatima R.; FRANCI, Andre; STRUNZ, Celia M. C.; ARANTES, Flavia B. B.; TAVONI, Thauany M.; RAMIRES, Jose A. F.; KALIL FILHO, Roberto; NICOLAU, Jose C.Background Patients with coronary artery disease (CAD) and previous ischemic cerebrovascular events (ICVE, ischemic stroke, or transitory ischemic attack) constitute a high-risk subgroup for cardiovascular outcomes. High-density lipoprotein cholesterol (HDL-C) levels are correlated with cardiovascular events. Lipid transfer to HDL affects structure size and HDL subclass profile. Impairment of this transfer could influence ischemic risk seen in patients with CAD + ICVE. The objective was to evaluate the HDL ability to receive the lipids in patients with CAD with or without ICVE. Methods Patients with CAD + ICVE (n = 60) and patients with CAD only (n = 60) were matched by age, sex, acute coronary syndromes (ACS) event type, and time elapsed between the ACS event and inclusion in the study. Lipid transfer to HDL was evaluated by incubating donor lipid nanoparticles labeled with radioactive unesterified cholesterol (UC) and esterified cholesterol (EC), phospholipid (PL), and triglyceride (TG) with whole plasma. After the chemical precipitation of non-HDL fractions and nanoparticles, the supernatant was counted for HDL radioactivity. Results CAD + ICVE group presented with impaired lipid transfer to HDL for PL (CAD + ICVE: 21.14 +/- 2.7% vs CAD: 21.67 +/- 3.1%, P = .03), TG (CAD + ICVE: 4.88 +/- 0.97% vs CAD: 5.63 +/- 0.92%, P = .002), and UC (CAD + ICVE: 5.55 +/- 1.19% vs CAD: 6.16 +/- 1.14%, P = .009). Lipid transfer to HDL was similar in both groups for EC. Adjusted models showed similar results. Conclusion Patients with CAD and ICVE have reduced lipid transfer to HDL compared to those with CAD only. Dysfunctional HDL may account for the higher incidence of ischemic outcomes observed in this population.
conferenceObject Effect of Exercise-based Cardiac Rehabilitation After Acute Myocardial Infarction on HDL Function: A Randomized Clinical Trial(2019) DALCOQUIO, Talia F.; FREITAS, Fatima; ARANTES, Flavia B.; FERREIRA-SANTOS, Larissa; ALVES, Leandro; SANTOS, Mayara; RONDON, Maria Urbana P.; ALVES, Maria-janieire N.; FURTADO, Remo H.; NEGRAO, Carlos E.; MARANHAO, Raul C.; NICOLAU, Jose C.- Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis(2019) BACHI, Andre L. L.; BARROS, Marcelo P.; VIEIRA, Rodolfo P.; ROCHA, Gislene A.; ANDRADE, Paula B. M. de; VICTORINO, Angelica B.; RAMOS, Luiz R.; GRAVINA, Claudia F.; LOPES, Jose D.; VAISBERG, Mauro; MARANHAO, Raul C.Cardiovascular benefits for the general population of combined aerobic-resistance exercise training are well-known, but the impact of this exercise training modality on the plasma lipid, inflammatory, and antioxidant status in elderly women that are exposed to a great risk of developing ischemic cardio- and cerebrovascular diseases has not been well investigated. So, we aimed to evaluate the plasma lipids, oxidative stress, and inflammatory cytokines in 27 elderly women (TRAINED group, 69.1 +/- 8.1yrs) that were performing moderate intensity combined aerobic-resistance exercise training (3 times/week for at least 18 months) and in 27 sedentary elderly women (SED group, 72.0 +/- 6.4yrs), not submitted to exercise training for at least 5yrs. Our results showed that BMI was lower in the TRAINED group than in the SED group (25.1 +/- 3.2 vs. 28.7 +/- 5.1, p<0.05). The TRAINED group had lower glycemia (92 +/- 3 vs. 118 +/- 12, p<0.05), glycated hemoglobin (5.9 +/- 0.1 vs. 6.4 +/- 0.2, p<0.05), and triglycerides (98 (75-122) vs. 139 (109-214), p<0.01); equal total cholesterol (199 (175-230) vs. 194 (165-220)), LDL-cholesterol (108 (83-133) vs. 109 (98-136)), and non-HDL-cholesterol (54 (30-74) vs. 62 (26-80)); and also higher HDL-cholesterol (64 (52-77) vs. 52 (44-63), p<0.01) and LDL-C/oxLDL ratio (13378 +/- 2570 vs. 11639 +/- 3113, p<0.05) compared to the SED group. Proinflammatory cytokines as IL-1 beta (11.31 +/- 2.4 vs. 28.01 +/- 4.7, p<0.05), IL-6 (26.25 +/- 7.4 vs. 49.41 +/- 17.8, p<0.05), and TNF-alpha (25.72 +/- 2.8 vs. 51.73 +/- 4.2, p<0.05) were lower in the TRAINED group than in the SED group. The TRAINED group had lower total peroxides (26.3 +/- 7.4 vs. 49.0 +/- 17.8, p<0.05) and oxidized LDL (1551 +/- 50.33 vs. 1773 +/- 74, p<0.02) and higher total antioxidant capacity (26.25 +/- 7.4 vs. 49.41 +/- 17.8, p<0.001) compared to the SED group. In conclusion, in TRAINED women, BMI was lower, plasma lipid profile was better, plasma oxidative stress was diminished, and there was less expression of proinflammatory interleukins than in SED, suggesting that combined aerobic-resistance exercise training may promote the protection against the complications of ischemic cardio- and cerebrovascular disease in elderly women.
- Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model(2019) MENEGHINI, Bianca C.; TAVARES, Elaine R.; GUIDO, Maria C.; TAVONI, Thauany M.; STEFANI, Helio A.; KALIL-FILHO, Roberto; MARANHAO, Raul C.Chemotherapeutic agents used in cancer treatment associated to nanoparticles (LDE) that mimic the composition of low-density lipoprotein and buffer their toxicity can have strong anti-atherosclerosis action, as we showed in cholesterol-fed rabbits. Here, a novel preparation of docetaxel (DTX) carried in LDE was evaluated. Eighteen rabbits were fed 1% cholesterol during 8 weeks. After the first 4 weeks, 9 animals were treated for 4 weeks with intravenous LDE-DTX (1 mg/kg/week) and 9 with LDE only (controls) once a week for 4 weeks. Animals were then euthanized and the aortas were analyzed for morphometry, immunohistochemistry and Western blot. LDE-DTX treated group showed 80% reduction of atheroma area compared to controls. LDE-DTX treatment reduced in 60% the protein expression of macrophage marker CD68 and of MCP-1 in 80%. LDE-DTX pronouncedly lowered expression of pro-inflammatory markers NF-kappa B, TNF-alpha, IL-1 beta, IL-6 and von Willebrand factor and elicited 40% reduction in cell proliferation marker PCNA. The presence of smooth muscle cells in the intima was 85% smaller than in controls. Pro-apoptotic caspase 3, caspase 9, Bax, and anti-apoptotic Bcl-2 all were reduced by LDE-DTX. Protein expression of MMP-2 and MMP-9, TGF-beta and collagen 1 and 3 were also markedly lowered by the LDE-DTX treatment. Animals showed no hematological, hepatic or renal toxicity consequent to LDE-DTX treatment. In conclusion, LDE-DTX showed a wide array of strong effects on pro-inflammatory and proliferation-promoting factors that drive the lesion development. These findings and the lack of observable toxicity indicate that LDE-DTX can be a candidate for future clinical trials.