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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- 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.
- Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease(2020) SALSOSO, Rocio; DALCOQUIO, Talia F.; FURTADO, Remo H. M.; FRANCI, Andre; BARBOSA, Carlos J. D. G.; GENESTRETI, Paulo R. R.; STRUNZ, Celia M. C.; LIMA, Viviane; BARACIOLI, Luciano M.; GIUGLIANO, Robert P.; GOODMAN, Shaun G.; GURBEL, Paul A.; MARANHAO, Raul C.; NICOLAU, Jose C.Introduction Lipoprotein (a) [Lp(a)] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp(a) and platelet reactivity in primary and secondary prevention. Methods Lp(a) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp(a) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp(a) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow (TM) P2Y(12)assay. Platelet reactivity was also induced by arachidonic acid and collagen-epinephrine (C-EPI) and assessed by Multiplate (TM), platelet function analyzer (TM) 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp(a) < 50 mg/dL [median (IQR) 13.2 (5.8-27.9) mg/dL] and 102 (25.8%) had Lp(a) >= 50 mg/dL [82.5 (67.6-114.5) mg/dL],P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp(a) >= 50 mg/dL (249.4 +/- 43.8 PRU) versus Lp(a) < 50 mg/dL (243.1 +/- 52.2 PRU),P = 0.277. Similar findings were present in individuals with (P = 0.228) and without (P = 0.669) CAD, and regardless of the agonist used or method of analysis (allP > 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp(a) >= 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99-1.01),P = 0.590]. Conclusion In individuals with or without CAD, Lp(a) >= 50 mg/dL was not associated with higher platelet reactivity.
- Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin(2012) PESARO, Antonio Eduardo P.; SERRANO JR., Carlos V.; FERNANDES, Juliano L.; CAVALCANTI, Alexandre B.; CAMPOS, Alexandre H.; MARTINS, Herlon S.; MARANHAO, Raul C.; LEMOS, James A. de; SOUZA, Heraldo P.; NICOLAU, Jose C.Background: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. Objective: We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10 mg/simvastatin 20 mg (E10/S20) with simvastatin 80 mg (S80). Methods and results: CAD patients (n = 83, 63 +/- 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 +/- 13% vs. 28 +/- 30%, p = 0.46), apo-B (18 +/- 17% vs. 22 +/- 15%, p = 0.22) and oxidized LDL (15 +/- 33% vs. 18 +/- 47%, p = 0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 +/- 43% vs. 8 +/- 33%, p = 0.02). Conclusions: These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4x less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80.
- Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles: a magnetic resonance imaging study(2017) LIMA, Aline D.; HUA, Ning; MARANHAO, Raul C.; HAMILTON, James A.Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel (4 mg/kg) while 7 controls received saline solution. On week 12 and 16, in vivo MRI of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction of atherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area (14%) and stenosis (22%) by MRI and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.
- Obstructive sleep apnea and effects of continuous positive airway pressure on triglyceride-rich lipoprotein metabolism(2018) DRAGER, Luciano F.; TAVONI, Thauany M.; SILVA, Vanessa M.; SANTOS, Raul D.; PEDROSA, Rodrigo P.; BORTOLOTTO, Luiz A.; VINAGRE, Carmen G.; POLOTSKY, Vsevolod Y.; LORENZI-FILHO, Geraldo; MARANHAO, Raul C.This study aimed to explore lipoprotein metabolism in obstructive sleep apnea (OSA) and the effects of continuous positive airway pressure (CPAP). We studied 15 men with severe OSA [apnea-hypopnea index (AHI) >= 30 events/hour] and 12 age-, BMI-, and waist circumference-matched volunteers without OSA (AHI <5 events/hour). Carotid intima-media thickness (CIMT) was determined by a blind examiner. After 12 h fasting, a triglyceride-rich chylomicron-like emulsion, labeled with [C-14]cholesteryl oleate and [H-3]triolein, was injected intravenously followed by blood sample collection at preestablished times. Fractional clearance rate (FCR) of the radiolabeled lipids was estimated by compartmental analysis of radioisotope decay curves. Compared with controls, patients with OSA showed a significant delay in both cholesteryl ester FCR (0.0126 +/- 0.0187 vs. 0.0015 +/- 0.0025 min(-1); P = 0.0313) and triglycerides FCR (0.0334 +/- 0.0390 vs. 0.0051 +/- 0.0074 min(-1); P = 0.0001). CIMT was higher in the OSA group: 620 +/- 17 vs. 725 +/- 29 mu m; P = 0.004. Cholesteryl ester FCRs were inversely related to total sleep time <90% (r = -0.463; P = 0.029) and CIMT (r = -0.601; P = 0.022). The triglyceride FCR was inversely correlated with AHI (r = -0.537; P = 0.04). In a subgroup of patients treated with CPAP for 3 months (n = 7), triglyceride FCR increased 5-fold (P = 0.025), but the cholesteryl ester FCR was unchanged. In conclusion, severe OSA decreased lipolysis of triglyceride-rich lipoproteins and delayed removal of remnants. CPAP treatment may be effective to restore the lipolysis rates.
- CHYLOMICRON METABOLISM IS IMPAIRED IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA: EFFECTS OF TREATMENT WITH CONTINUOUS POSITIVE AIRWAY PRESSURE(2018) DRAGER, L. F.; TAVONI, T. M.; SILVA, V. M.; SANTOS, R. D.; PEDROSA, R. P.; BORTOLOTTO, L. A.; VINAGRE, C. G.; POLOTSKY, V. Y.; LORENZI-FILHO, G.; MARANHAO, R. C.
- HDL acceptor capacities for cholesterol efflux from macrophages and lipid transfer are both acutely reduced after myocardial infarction(2018) SOARES, Alexandre A. S.; TAVONI, Thauany M.; FARIA, Eliane C. de; REMALAY, Alan T.; MARANHAO, Raul C.; SPOSITO, Andrei C.Background: The transport of lipids from the artery wall is one of the most essential anti-atherogenic functions of high-density lipoprotein (HDL). Recent reports of changes in the HDL composition, during myocardial infarction (MI), suggest that this function may be altered. Methods: Forty-one consecutive patients with ST-segment elevation MI enrolled at the Brasilia Heart Study were selected. The following HDL-related measures were determined upon admission (D1) and on the fifth day (D5) after MI: C-reactive protein, CETP and PLTP activity, HDL composition, efflux of cholesterol from J774 macrophages to HDL, and transfer of unesterified and esterified cholesterol, triglycerides and phospholipids from a donor nanoemulsion to HDL. Results: From D1 to D5, the activity of CETP decreased by 25%, but PLTP activity remained unchanged. Esterified cholesterol (-23%) and phospholipid (-9.5%) contents of HDL decreased. Transfer of triglycerides (-36.5%) and esterified cholesterol (-14.7%) to HDL from nanoemulsions was reduced, but other lipids transfers were unchanged. Cholesterol efflux to HDL was also diminished by 8.5% (p = 0.04) on D5 compared to D1. It was more pronounced in patients above the 75th percentile of C-reactive protein. Conclusions: After an MI, a simultaneous decrease in lipid transfer to HDL and in the capacity of HDL to efflux cholesterol from cells occurs. Thus, HDL with inferior atheroprotective properties may be generated in the acute post-MI period.
- PLASMA KINETICS OF CHYLOMICRON IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA: EFFECTS OF TREATMENT WITH CONTINUOUS POSITIVE AIRWAY PRESSURE(2018) DRAGER, Luciano F.; TAVONI, Thauany M.; SILVA, Vanessa M.; SANTOS, Raul D.; PEDROSA, Rodrigo P.; BORTOLOTTO, Luiz A.; VINAGRE, Carmen G.; POLOTSKY, Vsevolod Y.; LORENZI-FILHO, Geraldo; MARANHAO, Raul C.
conferenceObject The metabolism of triglyceride-rich lipoproteins is impaired in patients with obstructive sleep apnoea: effects of treatment with continuous positive airway pressure(2017) DRAGER, L. F.; SILVA, V. M.; TAVONI, T. M.; SANTOS, R. D.; PEDROSA, R. P.; BORTOLOTTO, L. A.; VINAGRE, C. G. C.; POLOTSKY, V. Y.; LORENZI-FILHO, G.; MARANHAO, R. C.