RAUL CAVALCANTE MARANHAO

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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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Autor e Coautores FMUSP-HC Normalizados: MARIA CAROLINA GUIDO ×

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Agora exibindo 1 - 10 de 29
  • article 0 Citação(ões) na Scopus
    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 Cavalcante
    Atherosclerosis 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
    LIPID CORE NANOPARTICLES AS VEHICLE FOR DOCETAXEL REDUCES ATHEROSCLEROTIC LESION, INFLAMMATION, CELL DEATH AND PROLIFERATION IN AN ATHEROSCLEROSIS RABBIT MODEL
    (2018) MENEGHINI, Bianca C.; TAVARES, Elaine R.; GUIDO, Maria C.; TAVONI, Tauany M.; KALLIL FILHO, Roberto; MARANHAO, Raul C.
  • conferenceObject
    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
  • article 2 Citação(ões) na Scopus
    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 Cavalcante
    In 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.
  • conferenceObject
    Methotrexate associated with a lipid core nanoparticle prevented the dilation and dissection of the aortic arch in mice with Marfan syndrome
    (2020) GUIDO, M. C.; LOPES, N. M.; I, C. Albuquerque; TAVARES, E. R.; JENSEN, L.; V, L. Pereira; KALIL-FILHO, R.; LAURINDO, F. R. M.; MARANHAO, R. C.
  • article 5 Citação(ões) na Scopus
    The Expression of Lipoprotein Receptors Is Increased in the Infarcted Area After Myocardial Infarction Induced in Rats With Cardiac Dysfunction
    (2018) LIMA, Aline D. de; GUIDO, Maria C.; TAVARES, Elaine R.; CARVALHO, Priscila O.; MARQUES, Alyne F.; MELO, Marcelo D. T. de; SALEMI, Vera M. C.; KALIL-FILHO, Roberto; MARANHAO, Raul C.
    Left ventricular (LV) remodeling after myocardial infarction constitutes the structural basis for ventricular dysfunction and heart failure. The characterization underlying the expression of lipoprotein receptors in cardiac dysfunction is scarcely explored. The aim of this study was to analyze the status of lipoprotein receptors on the infarcted and noninfarcted areas of LV and to verify whether nano particles that mimic the lipid structure of low-density lipoprotein (LDL) and have the ability to bind to LDL receptors (LDE) are taken up more avidly by the noninfarcted LV. 13 male Wistar rats with left coronary artery ligation (myocardial infarction [MI]) and 12 animals with SHAM operation (SHAM) were used in this study. 6 weeks after the procedure, the quantification of low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), scavenger receptor-class B type I (SR-BI) lipoprotein receptors, and PCNA proliferation marker, and tissue uptake of radioactively labeled LDE were performed. Immunohistochemistry and Western blot analysis showed that LDLR, LRP1, SR-BI, and PCNA, expression in infarcted area of MI was remarkably higher than SHAM and noninfarcted subendocardial (SEN) and interstitial (INT) areas. In addition, in SEN noninfarcted area of MI, the presence of LDLR was about threefold higher than in SHAM SEN and INT noninfarcted areas. The LDE uptake of noninfarcted LV of MI group was about 30% greater than that of SHAM group. In conclusion, these findings regarding the status of lipoprotein receptors after MI induction could help to establish mechanisms on myocardial repairing. In conclusion, infarcted rats with LV dysfunction showed increased expression of lipoprotein receptors mainly in the infarcted area.
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    METHOTREXATE CARRIED IN LIPID CORE NANOPARTICLES REDUCED THE INFARCTION SIZE AND IMPROVED LEFT VENTRICLE FUNCTION FOLLOWING ACUTE MYOCARDIUM INFARCTION INDUCED IN RATS
    (2017) MARANHAO, Raul Cavalcante; GUIDO, Maria Carolina; MARQUES, Alyne Franca; TAVARES, Elaine Rufo; BISPO, Deborah Lima; MELO, Marcelo Dantas Tavares De; LIMA, Aline Derisio; NICOLAU, Jose Carlos; SALEMI, Vera Maria; KALIL-FILHO, Roberto
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    Methotrexate reduces cardiac remodeling and improves left ventricle function in rats with Takotsubo cardiomyopathy
    (2019) GUIDO, M. C.; LOPES, N. M.; TAVARES, E. R.; BISPO, D. L.; MELO, M. D. Tavares De; SALEMI, V. M. C.; MARANHAO, R. C.
  • conferenceObject
    EFFECT OF EXERCISE TRAINING ON THE CAPACITY OF HDL TO RECEIVE UNESTERIFIED AND ESTERIFIED CHOLESTEROL AND ON PARAOXONASE 1 ACTIVITY IN AGED INDIVIDUALS
    (2022) BRAGA, P. G. S.; TAVONI, T. M.; BARONI, R. V.; FREITAS, F. R.; GUIDO, M. C.; ALVES, M. J. N. N.; ROCHA, G. A.; BACHI, A. L. L.; NEGRAO, C. E.; VAISBERG, M. W.; MARANHAO, R. C.
  • article 29 Citação(ões) na Scopus
    Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice
    (2016) KRETZER, Iara F.; MARIA, Durvanei A.; GUIDO, Maria C.; CONTENTE, Thais C.; MARANHAO, Raul C.
    Purpose: Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL) receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva), which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX). Materials and methods: B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 mu mol/kg (three intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9 consecutive days. Results: Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion: Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX.