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
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- 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.
- 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.
conferenceObject RELATIONSHIPS BETWEEN HDL FUNCTIONAL CHARACTERISTICS AND ENDOTHELIAL VASCULAR FUNCTION AFTER SHORT-TERM EXERCISE TRAINING IN PATIENTS WITH THE METABOLIC SYNDROME(2013) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; DOURADO, Paulo; LEITE-JUNIOR, Antonio C.; JONKE, Vivian; SEGRE, Alexandre; SANTOS, Raul; NEGRAO, Carlos E.; MARANHAO, Raul C.; CHAGAS, AntonioIntroduction: Endothelial dysfunction, leading to vasodilation impairment and atherosclerosis, frequently affects patients with metabolic syndrome (MS). A recent study showed that HDL estimulates endothelial nitric oxide synthase (eNOS: a key regulator of vascular nitric oxide production) by activation of Akt and MAP kinases in cultured endothelial cells. Objectives: To investigate the relationships between HDL characteristics (concentration, composition, functionality) on the eNOS availability and endothelial vascular function in patients with MS after a short-term exercise training (T). Methods: Forty sedentary persons (30 MS and 10 controls) were studied. Twenty with MS were subjected to a 3 times/week of a training load (45min/d) for 3 months on a bicycle. Cyclic guanosine monophosphate (cGMP), blood nitrite concentrations (biomarkers of eNOS availability) and HDL subfractions obtained by plasma ultracentrifugation were analyzed. A control LDL was incubated with HDL subfractions from the patients with MS (before-after T) and the in vitro resistance to oxidation was verified. An artificial radio-labeled lipoprotein emulsion was incubated with plasma from the participants. After precipitation of VLDL and LDL, the HDL containing supernatant was counted for radioactivity, to verify the HDL ability to accept lipids. Endothelial vascular function was assessed from forearm blood flow-mediated responses to vasodilation tests (FMD). Results: T did not change HDL-C concentration but changed the molecular composition and improved the functional characteristics of the HDL-particles subfractions: protecting LDL against oxidation (+21%) and increasing the HDL-particles ability to accept lipids (+23%). T increased cGMP and blood nitrite concentrations. The best HDL functional results were associated with the highest cGMP and blood nitrite concentrations and with the best FMD improvement results in the MS group. Conclusions: T early changes functional characteristics of HDL-particles, rather than HDL-C concentration, associated with eNOS biomarkers and with endothelial vascular function improvement in patients with MS, highlighting the early vascular benefits of exercising- 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.
conferenceObject In vitro transfer of lipids to high density lipoprotein (HDL) and carotid artery intima-media thickness in individuals with marked hyperalphalipoproteinemia(2016) LAURINAVICIUS, A. G.; PASSARELLI, M.; NAKANDAKARE, E.; HONG, V.; BORTOLOTTO, L.; BITTENCOURT, M. S.; CONCEICAO, R. O. D.; SANTOS, R. D.; MARANHAO, R.conferenceObject Predisposing factors to acute pancreatitis in patients with severe hypertriglyceridemia(2020) JULIANI, F. C.; MINAME, M. H.; CHACRA, A. P. M.; SALGADO, W.; MARANHAO, R. C.; SANTOS, R. D.; ROCHA, V. Z.- The removal from plasma of chylomicrons and remnants is reduced in heterozygous familial hypercholesterolemia subjects with identified LDL receptor mutations: Study with artificial emulsions(2012) CARNEIRO, Marcia M.; MINAME, Marcio H.; GAGLIARDI, Ana C.; PEREIRA, Carolina; PEREIRA, Alexandre C.; KRIEGER, Jose E.; MARANHAO, Raul C.; SANTOS, Raul D.Chylomicron remnants bind to both their specific receptors (LRP) and to the LDL receptor (LDLR) in the liver. There is controversy whether disturbances of chylomicron metabolism occur in subjects with familial hypercholesterolemia (FH). The aim of this study was to evaluate whether there are defects on the removal from plasma of chylomicrons and their remnants in heterozygous FH patients with determined LDLR mutations. We studied 20 heterozygous FH patients (43.2 +/- 12 years old, 60% males) and 50 normolipidemic subjects matched for age and gender. FH subjects were not in use of LDL-lowering drugs for at least 6 weeks. The removal from plasma of chylomicrons and their remnants was measured by isotopic decay after venous injection of a chylomicron-like emulsion radiolabeled with C-14-cholesteryl ester (C-14-CE) and H-3-triolein (H-3-TO). These track respectively removal from plasma of chylomicrons and remnants and lipolysis. There was a significant reduction in the fractional catabolic rates (FCR in h(-1)) of C-14-CE in FH in comparison with normolipidemics: 0.048 (1.46.10-7; 0.57) vs. 0.71(0.049; 1.62), [median (25th-75th percentile)], p = 0.003. No differences were found in FCR of H-3-TO between FH and controls, respectively 1.62 (1.02; 2.331) and 1.914 (1.34; 2.878), p = 0.405. In conclusion heterozygous FH subjects had a significant decrease on the removal from plasma of chylomicrons and their remnants compared with normolipidemics.
conferenceObject SHORT-TERM EXERCISE TRAINING CHANGES TRIGLYCERIDES MOLECULAR CONTENT OF THE LDL AND HDL PARTICLES AFFECTING THEIR FUNCTIONAL CHARACTERISTICS IN METABOLIC SYNDROME(2013) CASELLA-FILHO, Antonio; TROMBETTA, Ivani; DOURADO, Paulo Magno; LEITE-JUNIOR, Antonio Carlos; SPRANDEL, Marilia C. O.; SEGRE, Alexandre; SANTOS, Raul; NEGRAO, Carlos Eduardo; MARANHAO, Raul C.; CHAGAS, AntonioBackground: Long–term exercise training associated with diet changes lipoproteins plasma levels. Objectives: We sought to investigate the effects of short–term exercise training without any specific diet (T) on the concentration, composition and functional characteristics of LDL and HDL particles in patients with metabolic syndrome (MS). Methods: Forty sedentary persons (30 MS and 10 controls) were studied. 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 and their compositions were analyzed. The in vitro resistance to oxidation of the LDL from the patients with MS (before and after T) was verified. A control LDL was incubated with HDL2a and HDL3b from the patients with MS (before – after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C–phospholipid, 3H–triglycerides, 14C–cholesterol and 3H–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. Results: T decreased triglycerides (TG) but did not change LDL–C and HDL–C plasma levels. The LDL resistance to oxidation of the MS group increased (+91%) after T, associated with a significant decrease in the LDL–particles content of TG (−14%) and apoB (−16%), and with a 27% reduction of the small and dense LDL–particles plasma levels. The oxidizability of the control LDL decreased when mixed with HDL2a or HDL3b from patients with MS, before vs. after T (−23% for HDL2a and −18% for HDL3b) associated with a significant decrease in the content of TG in HDL3b (−12%) and HDL3c (−15%). The transference of TG to HDL normalized after T in the MS group. Conclusions: In patients with MS, T early reduces TG concentration influencing the LDL and HDL functionality by changing their molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating lipoproteins composition and functional aspects besides their plasma levels.- Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with familial hypercholesterolemia(2013) MARTINEZ, Lilton R. C.; SANTOS, Raul D.; MINAME, Marcio H.; DEUS, Debora F.; LIMA, Emerson S.; MARANHAO, Raul C.Objective. In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in PH patients. Methods. Seventy-one PH patients (39 +/- 15 years, LDL-cholesterol = 274 +/- 101; HDL-cholesterol = 50 +/- 14 mg/di) and 66 normolipidemic subjects (NL) (38 +/- 11 years, LDL-cholesterol = 105 +/- 27; HDL-cholesterol = 52 +/- 12 mg/dl) were studied. In vitro, lipid transfers were evaluated by incubation of plasma samples (37 degrees C, 1 h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total radioactivity measured in the HDL fraction. Results. Transfer of UC to HDL was lower in FH than in NL (5.6 +/- 2.1 vs 6.7 +/- 2.0%, p = 0.0005) whereas TG (5.5 +/- 3.1 vs 3.7 +/- 0.9%, p = 0.018) and PL (20.9 +/- 4.6 vs 18.2 +/- 3.7 %, p = 0.023) transfers were higher in FH. EC transfer was equal. By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I. Conclusion. FH elicited marked changes in three of the four tested lipid transfers to HDL. The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease. Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.
conferenceObject Cardiovascular Disease Progression in Children With Homozygous Familial Hypercholesterolemia Despite Early Diagnosis on a Genetic Cascade Screening Program(2022) JULIANI, Fabiana C.; CHACRA, Ana Paula M.; MINAME, Marcio H.; SALGADO FILHO, Wilson; MIZUTA, Marjorie H.; JANNES, Cinthia E.; KRIEGER, Jose E.; MARANHAO, Raul C.; SANTOS, Raul D.; ROCHA, Viviane Z.