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
20 resultados
Resultados de Busca
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- Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE)(2023) ALBUQUERQUE, Camila Inagaki; TAVARES, Elaine Rufo; GUIDO, Maria Carolina; CARVALHO, Priscila Oliveira; TAVONI, Thauany Martins; LOPES, Natalia Menezes; SILVA, Bruna Miranda de Oliveira; JENSEN, Leonardo; STOLF, Noedir Antonio Groppo; MARANHA, Raul CavalcanteAtherosclerosis is a cell-proliferative, chronic inflammatory process. The aim was to investigate whether lipid core nanoparticles (LDE) carrying the anti-cancer agent daunorubicin could have anti-atherosclerotic effects. LDE is taken-up by cellular lipoprotein receptors and is capable of concentrating incorporated drugs in inflammed tissues. New Zealand male rabbits were fed 1% cholesterol diet for 8 weeks. Then, animals were treated with LDE-daunorubicin (6 mg/kg/week, IV, n = 9) or with LDE only (n = 7). Atherosclerotic lesions in LDE-daunorubicin group were 50% smaller than in LDE group. In LDE-daunorubicin, protein expressions of the pro-inflammatory markers CD68, TNF-alpha IL-6 and gene expression MCP-1 were lower than in LDE. Gene expression of IL-1 beta, IL-18 and IL-10 were similar. Protein expressions of VEGF and of pro-apoptotic caspase 3, caspase 9 and BAX, and both protein and gene expressions of VCAM-1 were all lower in LDE-daunorubicin. Gene expression of MMP-12 and protein expression of MMP-2 were lower in LDE-daunorubicin, but MMP-9 was not different. Daunorubicin is known as cardiotoxic, but at echocardiography, LDE-daunorubicin had no differences in arch aorta diameters, systolic and diastolic function and in cardiac hypertrophy compared to LDE group. LDEdaunorubicin was capable of reducing atherosclerotic lesions by different mechanisms without observable toxicities.
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.- Effect of paclitaxel and methotrexate associated with cholesterol-rich nanoemulsions on ischemiareperfusion injury after unilateral lung transplantation in rats(2023) BATTOCHIO, Angela; TAVARES, Elaine; CORREIA, Aristides; ALMEIDA, Francine; CARVALHO, Priscila; GUIDO, Maria; PEGO-FERNANDES, Paulo; MARANHAO, Raul; PAZETTI, Rogerio
- 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.
- Decellularized Splenic Matrix as a Scaffold for Spleen Bioengineering(2020) ZANARDO, Tadeu Eriton Caliman; AMORIM, Fernanda Gobbi; TAUFNER, Gabriel Henrique; PEREIRA, Rayssa Helena Arruda; BAIENSE, Ian Manhoni; DESTEFANI, Afranio Cogo; IWAI, Leo Kei; MARANHAO, Raul Cavalcante; NOGUEIRA, Breno ValentimThe spleen is considered a non-essential organ. However, its importance is increasingly clear, given the serious disorders caused by its absence or dysfunction, e.g., greater susceptibility to infections, thromboembolism and cancer. Surgical techniques to preserve the spleen and maintain splenic function have become increasingly common. However, the morbidity and mortality associated with its absence and dysfunction are still high. We used the decellularization technique to obtain a viable splenic scaffold for recellularizationin vitroand propose the idea of bioengineered spleen transplantation to the host. We observed the maintenance of important structural components such as white pulp, marginal zone and red pulp, in addition to the network of vascular ducts. The decellularized scaffold presents minimal residual DNA and SDS, which are essential to prevent immunogenic responses and transplantation failure. Also, the main components of the splenic matrix were preserved after decellularization, with retention of approximately 72% in the matrisomal protein content. The scaffold we developed was partially recellularized with stromal cells from the spleen of neonatal rats, demonstrating adhesion, proliferation and viability of cells. Therefore, the splenic scaffold is very promising for use in studies on spleen reconstruction and transplantation, with the aim of complete recovery of splenic function.
- 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
- 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.
- Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study(2024) MARINHO, Lucas Lage; RACHED, Fabiana Hanna; MORIKAWA, Aleksandra Tiemi; TAVONI, Thauany Martins; CARDOSO, Ana Paula Toniello; TORRES, Roberto Vitor Almeida; JR, Antonildes Nascimento Assuncao; JR, Carlos Vicente Serrano; NOMURA, Cesar Higa; MARANHAO, Raul CavalcanteIntroduction Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease.Methods We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment.Results Forty patients aged 65.6 +/- 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed.Conclusion In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers.Clinical Trial Registration https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
conferenceObject Methotrexate associated with nanoparticles decreases NLRC4 inflammasome expression in infarcted rat hearts(2023) GATTO, M.; MOTA, G. A. F.; BORIM, P. A.; SANTOS, A. C. C.; PAGAN, L. U.; SOUZA, L. M.; RODRIGUES, E. A.; SILVA, R. C. F.; OLIVEIRA, J. P. G.; MEIRELLES, A. L. B.; BROSLER, J. Y.; MARANHAO, R. C.; ZORNOFF, L. A. M.; OKOSHI, K.; OKOSHI, M. P.- Changes in serum amyloid A, plasma high- density lipoprotein cholesterol and apolipoprotein A- I as useful biomarkers for Mycobacterium tuberculosis infection(2023) FONTES, Cleuber Franco; BIDU, Nadielle Silva; FREITAS, Fatima Rodrigues; MARANHAO, Raul Cavalcante; MONTEIRO, Adriano de Souza Santos; COUTO, Ricardo David; NETTO, Eduardo MartinsIntroduction. In recent years, cholesterol has received interest in the study of infection due to evidence of a relationship between low plasma cholesterol levels and tuberculosis (TB). Hypothesis/Gap Statement. Plasma lipid profiles of serum amyloid A (SAA), apolipoprotein A -I and high-density lipoprotein cholesterol (HDL- C) are biomarkers associated with symptomatic TB patients. Objective. We aimed to evaluate plasma lipid profiles of apolipoprotein A -I, SAA and the size of HDL as biomarkers to diagnose symptomatic TB patients. Methodology. Patients with TB symptoms attending the Instituto Brasileiro para a Investigacao da Tuberculose/Fundacao Jose Silveira (IBIT/FJS) between September 2015 and August 2016 for diagnosis of TB were studied. From 129 patients, 97 were classified as pulmonary TB and 32 as negative-bacilloscopy (non -TB group). Medical history, fasting serum and plasma were obtained. Total cholesterol (TC), HDL- C, apolipoprotein A -I and SAA were measured by enzymatic or immunochemical reaction assays. HDL size was measured by laser light-scattering. Results. In TB patients, TC (147.0 & PLUSMN;37 vs. 168 & PLUSMN;44 mg dL-1), HDL- C (37 & PLUSMN;14 vs. 55 & PLUSMN;18 mg dL-1) and apolipoprotein A -I (102 & PLUSMN;41 vs. 156 & PLUSMN;47 mg dL-1) concentrations were lower (P<0.0001), while HDL particle size (10.16 & PLUSMN;1.02 vs. 9.62 & PLUSMN;0.67 nm) and SAA levels (280 & PLUSMN;36 vs. 19 & PLUSMN;8 mg L-1) were higher (P<0.0001). Using receiver-operating characteristic curve analysis for predicting TB, the cutoff values were <83.85 mg L-1 for SAA (sensitivity=96.88 %, specificity=78.43 %, P<0.0001), >44.50 mg dL-1 for HDL- C (sensitivity=75%, specificity=72.16%, P<0.001) and >118.5 mg dL-1 for apolipoprotein A -I (sensitivity=83.83 %, specificity=72.22 %, P<0.001). Conclusion. SAA, HDL- C and apolipoprotein A -I are associated with TB infection and could be used as laboratory biomarkers, especially in patients who are negative for alcohol- acid-resistant bacilli.