NATALIA DE MENEZES LOPES
Projetos de Pesquisa
Unidades Organizacionais
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- 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.
- 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.
conferenceObject Methotrexate Carried in Lipid Core Nanoparticles Prevented the Dilation and Dissection of the Aortic Arch in Mice With Marfan Syndrome by Increasing the Bioavailability of Intracellular Adenosine(2020) GUIDO, Maria Carolina; LOPES, Natalia M.; ALBUQUERQUE, Camila I.; TAVARES, Elaine R.; JENSEN, Leonardo; PEREIRA, Lygia V.; LAURINDO, Francisco R.; MARANHAO, Raul C.conferenceObject Daunorubicin Associated With Lipid Nanoparticles Reduces Inflammation and Aortic Lesions in an Atherosclerosis Rabbit Model(2019) ALBUQUERQUE, Camila I.; TAVARES, Elaine R.; GUIDO, Maria Carolina; LOPES, Natalia M.; BARONI, Roberta Vanalli; JENSEN, Leonardo; SILVA, Bruna M. Araujo; KALIL, Roberto; TAVONI, Thauany M.; MARANHAO, Raul C.conferenceObject Left Ventricle Dysfunction is Prevented by the Treatment With Methotrexate Carried in Lipid Nanoparticles in Lipopolysaccharide-injected Rats(2020) LOPES, Natalia M.; GUIDO, Maria Carolina; ALBUQUERQUE, Camila; JENSEN, Leonardo; MARANHAO, Raul C.conferenceObject Lipid Transfer to High Density Lipoproteins is Impaired and Cholesteryl Ester Transfer Protein Plasma Concentration is Diminished in Patients With Peripheral Arterial Disease(2019) LOPES, Natalia M.; RIBEIRO, Flavio R.; AZEVEDO, Carolina H.; TAVONI, Thauany M.; SARGES, Erica S.; FREITAS, Fatima R.; ALBUQUERQUE, Camila; KALIL, Roberto; MARANHAO, Raul C.