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
22 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 22
conferenceObject LIPIDS TRANSFER TO HDL IN PATIENTS WITH HEART FAILURE WAS DIMINISHED AND IS CORRELATED WITH IL-6 AND BNP LEVELS(2017) MARTINE, Ana Elisa Marabini; CARVALHO, Priscila O.; CURIATTI, Milena N. C.; MIRANDA, Bruna O.; FREITAS, Fatima R.; KALIL FILHO, Roberto; BARRETTO, Antonio Carlos Pereira; MARANHAO, Raul C.- Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions(2011) TAVARES, Elaine R.; FREITAS, Fatima R.; DIAMENT, Jayme; MARANHAO, Raul C.Objectives: Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated. Methods: Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections. Results: LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1 beta and tumor necrosis factor-alpha), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase II alpha and tubulin). Conclusion: The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.
- Lipoprotein removal mechanisms and aging: implications for the cardiovascular health of the elderly(2020) MARANHAO, Raul C.; PALA, Daniela; FREITAS, Fatima R.Purpose of review The speed of removal from the plasma of apolipoprotein B-containing lipoproteins, for example, chylomicrons, VLDL and LDL is determinant of the plasma concentration of these lipoproteins, is influenced by genetic features and ambient factors, and has implications in atherogenesis. As aging increases the clinical complications of atherosclerosis, it is important to appraise the status of the removal mechanisms in elderly individuals. Recent findings Removal of triglyceride-rich lipoproteins remnants is delayed but the triglyceride breakdown is unchanged in elderly individuals. The discovery of PCSK9, enzyme that degrades LDL receptors, and the recent observation that PCSK9 is elevated in the elderly raises another hypothesis to account for the increased LDL-cholesterol levels in the elderly. The removal of cholesterol from cells by HDL, the first step of cholesterol reverse transport is also less efficient in the elderly, which may compromise the body cholesterol homeostasis. Aging determines reduction of the efficiency of lipoprotein plasma removal mechanisms, which is implicated in increased incidence of cardia complications. Moreover, aging is frequently accompanied by physical activity reduction, weight gain, and metabolic disturbances that can further decrease the efficacy of the removal mechanisms. This knowledge is important for promoting cardiovascular health in the elderly and prolonging survival.
- An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: A study in a rabbit graft model(2011) LOURENCO-FILHO, Domingos D.; MARANHAO, Raul C.; MENDEZ-CONTRERAS, Carlos A.; TAVARES, Elaine R.; FREITAS, Fatima R.; STOLF, Noedir A.Objective: In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure. Methods: Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg . kg(-1) . d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake. Results: Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment. Conclusions: LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies. (J Thorac Cardiovasc Surg 2011;141:1522-8)
- Lipid transfers to HDL are predictors of precocious clinical coronary heart disease(2012) MARANHAO, Raul C.; FREITAS, Fatima R.; STRUNZ, Celia M.; SANTOS, Raul D.; MANSUR, Alfredo J.; MANSUR, Antonio P.Background: High-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function. Methods: Thirty normocholesterolemic CAD patients aged <50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol. cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL. Results: LDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8 +/- 1.2%vs 7.0 +/- 33%,p<0.0001) and triglycerides (3.7 +/- 1.7%vs 4.9 +/- 1.9%, p = 0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5 +/- 1.9%vs 4.8 +/- 1.8%, p = 0.0008); phospholipid transfer was equal (17.8 +/- 3.5% vs19.5 +/- 3.9%). Conclusion: Alterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies. (C) 2011 Published by Elsevier B.V.
- Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects(2018) VINAGRE, Carmen G.; FREITAS, Fatima R.; MESQUITA, Carlos H. de; VINAGRE, Juliana C.; MARIANI, Ana Carolina; KALIL-FILHO, Roberto; MARANHAO, Raul C.Dietary fats absorbed in the intestine are transported in the circulation as chylomicrons and remnants that have atherogenic potential. Although postprandial lipidemia is increased in older subjects, the specific chylomicron metabolism has not been explored in older subjects nor compared to young subjects, which is the focus of this study. After a 12 h fast, artificially-made emulsions similar to lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and triglycerides were intravenously injected in 23 older (66 +/- 4 years) and 20 young (24 +/- 3 years) subjects. Sequential blood samples were collected to determine fractional clearance rates (FCR, in min(-1)) by compartmental analysis. Older subjects had higher LDL-cholesterol (p<0.001) and triglycerides (p<0.0001) than young subjects; HDL-cholesterol presented no difference. The emulsion cholesteryl-ester FCR was lower in older subjects compared to the young (p=0.0001). The emulsion triglyceride FCR did not differ in the two groups. Tested in vitro, however, the lipolysis of the emulsion triglycerides was less intense in the older than in the young subjects. As delayed removal of remnants, indicated by the pronouncedly smaller cholesteryl ester FCR, is related to the presence of cardiovascular diseases, this can be a risk factor which could accelerate atherogenic complications occurring in aged subjects
- Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment(2013) FEITOSA, Alina C. R.; FEITOSA-FILHO, Gilson S.; FREITAS, Fatima R.; WAJCHENBERG, Bernardo L.; MARANHAO, Raul C.Background: Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels. Methods: Sixteen male patients with T1DM (26 +/- 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 +/- 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with C-14-cholesteryl ester and H-3-free-cholesterol for determination of fractional clearance rates (FCR, in h(-1)) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro. Results: LDL-cholesterol (83 +/- 15 vs 100 +/- 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker C-14-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 +/- 0.022 vs 0.039 +/- 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal. Conclusion: T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.
- Intraoperative paclitaxel associated with lipid nanoparticles in trabeculectomy(2023) OCCHIUTTO, Marcelo L.; PASSOS, Thais H. M.; FREITAS, Fatima R.; MARANHAO, Raul C.; COSTA, Vital P.
- 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 Lipid nanoemulsion associated with paclitaxel as a new antiscarring agent in experimental glaucoma surgery(2016) COSTA, Vital P.; OCCHIUTTO, Marcelo; FREITAS, Fatima R.; PICCIARELLI, Patricia; MARANHAO, Raul
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