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.conferenceObject Regression of atherosclerotic plaques of cholesterol-fed rabbits by combined chemotherapy of paclitaxel and methotrexate carried in lipid core nanoparticles(2017) GOMES, F. T. Torres; MARANHAO, R. C.; TAVARES, E. R.; CARVALHO, P. O.; MATTOS, F. R.; MACHADO, T.; HIGUCHI, M. L.; HATAB, S. A.; FILHO, R. Kalil; SERRANO JUNIOR, C. V.conferenceObject LIPID TRANSFER TO HDL IN PATIENTS WITH CORONARY ARTERY DISEASE(2014) SPRANDEL, Mar lia O.; HUEB, Whady; CASELLA-FILHO, Antonio; SCUDELER, Thiago; REZENDE, Paulo; LIMA, Eduardo; SEGRE, Alexandre; CARVALHO, Ana; MARANHAO, Raul; KALIL-FILHO, RobertoconferenceObject Anti-cellular Proliferation Therapy Reduces Atherosclerotic Plaques and Vascular Inflammation in Experimental Hypercholesterolemia(2016) GOMES, Fernando L.; MARANHAO, Raul C.; TAVARES, Elaine R.; OLIVEIRA, Priscila C.; MACHADO, Thiago V.; SOEIRO, Alexandre M.; HIGUCHI, Maria de Lourdes; KALIL-FILHO, Roberto; SERRANO, Carlos V.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 transfer to HDL, CETP and HDL composition in coronary artery disease patients with or without type 2 diabetes mellitus(2020) TAVONI, Thauany M.; SPRANDEL, Marilia C. O.; LAVERDY, Oscar G.; STRUNZ, Celia M. C.; RAMIRES, Jose A. F.; KALIL-FILHO, Roberto; HUEB, Whady A.; MARANHAO, Raul C.
conferenceObject Effect of exercise training on HDL subclasses and cholesterol transfers to HDL in elderly individuals(2022) BRAGA, P. G. Senger; TAVONI, T. M.; BARONI, R. V.; ALDIN, M. N.; ALVES, M. J. N. N.; ROCHA, G. A.; BACHI, A. L. L.; NEGRAO, C. E.; VAISBERG, M. W.; FREITAS, F. R.; FIGUEIREDO NETO, A. M.; DAMASCENO, N. R. T.; MARANHAO, R. C.- 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)
- Treatment With Methotrexate Associated With Lipid Core Nanoparticles Prevents Aortic Dilation in a Murine Model of Marfan Syndrome(2022) GUIDO, Maria Carolina; LOPES, Natalia de Menezes; ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; JENSEN, Leonardo; CARVALHO, Priscila de Oliveira; TAVONI, Thauany Martins; DIAS, Ricardo Ribeiro; PEREIRA, Lygia da Veiga; LAURINDO, Francisco Rafael Martins; MARANHAO, Raul CavalcanteIn Marfan syndrome (MFS), dilation, dissection, and rupture of the aorta occur. Inflammation can be involved in the pathogenicity of aortic defects and can thus be a therapeutic target for MFS. Previously, we showed that the formulation of methotrexate (MTX) associated with lipid nanoparticles (LDE) has potent anti-inflammatory effects without toxicity. To investigate whether LDEMTX treatment can prevent the development of aortic lesions in the MFS murine model. Mg Delta loxPneo MFS (n = 40) and wild-type (WT, n = 60) mice were allocated to 6 groups weekly injected with IP solutions of: (1) only LDE; (2) commercial MTX; (3) LDEMTX (dose = 1mg/kg) between 3rd and 6th months of life. After 12 weeks of treatments, animals were examined by echocardiography and euthanatized for morphometric and molecular studies. MFS mice treated with LDEMTX showed narrower lumens in the aortic arch, as well as in the ascending and descending aorta. LDEMTX reduced fibrosis and the number of dissections in MFS but not the number of elastic fiber disruptions. In MFS mice, LDEMTX treatment lowered protein expression of pro-inflammatory factors macrophages (CD68), T-lymphocytes (CD3), tumor necrosis factor-alpha (TNF-alpha), apoptotic factor cleaved-caspase 3, and type 1 collagen and lowered the protein expression of the transforming growth factor-beta (TGF-beta), extracellular signal-regulated kinases 1/2 (ERK1/2), and SMAD3. Protein expression of CD68 and CD3 had a positive correlation with an area of aortic lumen (r(2) = 0.36; p < 0.001), suggesting the importance of inflammation in the causative mechanisms of aortic dilation. Enhanced adenosine availability by LDEMTX was suggested by higher aortic expression of an anti-adenosine A2a receptor (A2a) and lower adenosine deaminase expression. Commercial MTX had negligible effects. LDEMTX prevented the development of MFS-associated aortic defects and can thus be a candidate for testing in clinical studies.