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
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conferenceObject Influence of the concentration and molecular composition on the LDL and HDL functional characteristics in patients with the metabolic syndrome(2012) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; CASELLA, Lia B.; DENARDI, Celise; DOURADO, Paulo; SEGRE, Alexandre; ROEVER-BORGES, Leonardo; NEGRAO, Carlos Eduardo; MARANHAO, Raul; CHAGAS, Antonio CarlosIntroduction: Long-term exercise associated with diet changes lipoproteins plasma levels. Objectives: We sought to analize the effects of short-term exercise training without any specific diet (T) on the concentration,composition and functional characteristics of LDL and HDL in patients with metabolic syndrome (MS). Methods: Forty sedentary persons were studied,30 with MS and 10 controls.Twenty of those with MS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer.LDL and HDL subfractions were obtained by plasma ultracentrifugation 1 and their compositions were analyzed. LDL from control subjects was incubated with HDL2a,HDL3b from the MS patients (before and after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C-phospholipid, 3 H-triglycerides, 14 C-cholesterol and 3 H-cholesteryl ester was incubated with plasma from the participants. After precipitation of VLDL, LDL and LDE the HDL-containing supernatant was counted for radioactivity to verify the HDL ability to accept lipids. 2 Results: T decreased triglycerides (TG) but did not change apoB,apoA-I,LDL-C and HDL-C plasma levels. LDL resistance to oxidation increased (+91%) after T,associated with a decrease in the LDL content of apoB (-16%) and TG (-14%) and in the concentration of the small and dense LDL particles. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MS, before vs. after T (-23% for HDL2a and -18% for HDL3b),associated with an increase in PON1 activity in the MS group (58.3±36.2 before vs.70.7±38.4ng/ml/min after T, p<0.05) and with a significant decrease in the content of total cholesterol (TC) and TG in HDL3b and HDL3c but with an increase in cholesterol ester (CE) in HDL3b. T did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a. Phospholipids and total protein content did not change in all HDL subfractions.T significantly increased free cholesterol and CE transfer from LDE to HDL in MS group to levels similar to those observed in controls. Conclusion: In patients with the MS, T influences the LDL and HDL functionality by earlier changes in molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating the functional aspects of the lipoproteins besides their plasma levelsconferenceObject 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.- Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance(2012) BERTATO, Marina P.; OLIVEIRA, Carolina P.; WAJCHENBERG, Bernardo L.; LERARIO, Antonio C.; MARANHAO, Raul C.OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with C-14-cholesteryl ester and H-3-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14 C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the H-3-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.
conferenceObject Paclitaxel Delivered With Nanoparticles Inhibits Neointimal Formation and Local Inflammation in Experimental Chronic Allograft Vasculopathy(2014) PEPINELI, R.; SANTANA, A.; TIEME, A.; DEUS, D.; MARANHAO, R.; NORONHA, I.- 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.
- Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects(2014) MANGILI, Otavio Celeste; GAGLIARDI, Ana C. Moron; MANGILI, Leonardo Celeste; MESQUITA, Carlos H.; CESAR, Luiz A. Machado; TANAKA, Akira; SCHAEFER, Ernst J.; MARANHAO, Raul C.; SANTOS, Raul D.Objective: Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients. Methods: 25 CHD patients were randomized for treatment with ezetimibe 10 mg (group 1) or simvastatin 20 mg (group 2) with progression to ezetimibe + simvastatin 10/20 mg or simvastatin 80 mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with C-14-CE and H-3-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA. Results: The (CE)-C-14-FCR in group 1 were 0.005 +/- 0.004, 0.011 +/- 0.008 and 0.018 +/- 0.005 min(-1) and in group 2 were 0.004 +/- 0.003, 0.011 +/- 0.008 and 0.019 +/- 0.007 min(-1) respectively at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). The H-3-TG-FCR in group 1 were 0.017 +/- 0.011, 0.024 +/- 0.011 and 0.042 +/- 0.013 min(-1) and in group 2 were 0.016 +/- 0.009, 0.022 +/- 0.009 and 0.037 +/- 0.012 min(-1) at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time. Conclusion: Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.
- Oxidized and electronegative low-density lipoprotein as potential biomarkers of cardiovascular risk in obese adolescents(2018) FREITAS, Maria Camila Pruper de; FERNANDEZ, Diana Gabriela Estevez; COHEN, Danielle; FIGUEIREDO-NETO, Antonio Martins; MARANHAO, Raul Cavalcante; DAMASCENO, Nagila Raquel TeixeiraOBJECTIVES: To evaluate biomarkers associated with early cardiometabolic risk in obese adolescents. METHODS: This cross-sectional study included 137 adolescents of both sexes aged 10 to 19 years divided into a normal weight group (NW) (n=69) and an obese group (OB) (n=68). RESULTS: As expected, obesity showed positive associations with homeostatic model assessment for insulin resistance (HOMA-IR), triacylglycerol, insulin, plasma levels of non-esterified fatty acids, and cholesterol ester transfer protein activity and negative associations with plasma antioxidant levels. Plasma oxidized low-density lipoprotein (oxLDL) and electronegative low-density lipoprotein [LDL(-)] levels were significantly higher in the OB group. Higher tertiles of oxLDL were associated with increased values of body mass index; waist circumference; fatty mass percentage (%FM); and the atherogenic lipids non-high-density-lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and triacylglycerol. Higher tertiles of LDL(-) were robustly associated with body mass index and waist circumference. Logistic regression models (odds ratios) confirmed that increased values of lipids and apolipoprotein B were associated with increased risk of oxLDL. For LDL(-), these associations were not significant, suggesting that another mechanism is involved in generating this particle in obese adolescents. CONCLUSIONS: Obese adolescents showed increased plasma LDL(-) and oxLDL, and obese girls had more LDL(-) than obese boys. Therefore, oxLDL is strongly and independently associated with classical cardiovascular risk factors, while increased levels of LDL(-) were influenced by body mass index, waist circumference and demographic parameters in obese adolescents.
- Organic effects of associating paclitaxel with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella(2017) FEIO, Danielle Cristinne Azevedo; OLIVEIRA, Nayara Cristina Lima de; PEREIRA, Edmundo Luis Rodrigues; MORIKAWA, Aleksandra Tiemi; MUNIZ, Jose Augusto Pereira Carneiro; MONTENEGRO, Raquel Carvalho; ALVES, Ana Paula Negreiros Nunes; LIMA, Patricia Danielle Lima de; MARANHAO, Raul Cavalcante; BURBANO, Rommel RodriguezLipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m(2)) and three with higher (250 mg/m(2)) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight-food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents.
- Pilot clinical study of carmustine associated with a lipid nanoemulsion in combination with vincristine and prednisone for the treatment of canine lymphoma(2015) LUCAS, S. R. R.; MARANHAO, R. C.; GUERRA, J. L.; COELHO, B. M. P.; BARBOZA, R.; POZZI, D. H. B.A lipid nanoemulsion (LDE) resembling low-density lipoprotein can target malignant tumours. In in vivo and clinical studies, association of chemotherapeutic agents to LDE decreased their toxicity and increased pharmacological action. Here, safety of LDE as carmustine carrier (50 mg m(-2), intravenous) combined with vincristine and prednisone for the treatment of dogs with lymphoma was tested and compared with commercial carmustine with vincristine and prednisone. In five dogs from LDE-carmustine and six from commercial carmustine, complete remission was achieved (P > 0.05). Partial remission occurred in two dogs from each group. In both groups, the median progression-free intervals (119 and 199 days) and overall survival times (207 and 247 days) were equal. Neutropenia was observed in both groups, but no other major toxicities occurred. Therefore, no difference was observed between the treatments. LDE-carmustine was shown to be safe and effective in a drug combination protocol, which encourages larger studies to investigate the use of this novel formulation to treat canine lymphomas.
- What is new in familial hypercholesterolemia?(2014) SANTOS, Raul D.; MARANHAO, Raul C.Purpose of reviewThe purpose of this review is to describe advances in the diagnosis, cause, metabolism, risk factors for atherosclerosis, and treatment of familial hypercholesterolemia.Recent findingsHeterozygous familial hypercholesterolemia is almost four-fold more frequent than previously thought and is associated with 10-fold to 13-fold risk of cardiovascular disease comparing with normolipidemics. LDL receptor (LDLR) dysfunction and LDL-cholesterol (LDL-C) accumulation disturb the metabolism of other lipoprotein classes, such as chylomicrons and remnants and HDL. Next-generation sequencing can improve familial hypercholesterolemia molecular diagnosis due to its better performance and lower costs than usual techniques. Despite this, roughly 40% of familial hypercholesterolemia patients do not present mutations on the LDLR, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9 genes. Many individuals with familial hypercholesterolemia phenotype have polygenic instead of monogenic cause of their elevated LDL-C concentrations. Individuals with familial hypercholesterolemia show elevated burden of subclinical atherosclerosis. The intensity of atherosclerosis burden is associated with the severity of LDLR mutation rather than maternal or paternal heritability. Newer-approved and on-development medications that reduce LDL-C hold promise for preventing cardiovascular disease in familial hypercholesterolemia.SummaryFamilial hypercholesterolemia is frequent and currently underdiagnosed and undertreated, but effective cascade screening programs and early and intensive LDL-C lowering can change this picture and the natural history of the disease.