ALYNE FRANCA MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- 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.
conferenceObject 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- Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model(2017) FIORELLI, A. I.; LOURENCO-FILHO, D. D.; TAVARES, E. R.; CARVALHO, P. O.; MARQUES, A. F.; GUTIERREZ, P. S.; MARANHAO, R. C.; STOLF, N. A. G.Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg.kg(-1).day(-1) orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.
conferenceObject Effects of treatment with methotrexate associated to lipid nanoparticles on diabetic cardiomyopathy in rats(2016) MARQUES, A. F.; GUIDO, M. C.; TAVARES, E. R.; BISPO, D. L.; MELLO, M. D.; SALEMI, V. M.; MARANHAO, R. C.conferenceObject Methotrexate carried in lipid nanoparticles pronouncedly improves the functional and inflammatory status of the heart following acute myocardium infarction induced in rats(2016) GUIDO, M. C.; MARQUES, A. F.; TAVARES, E. R.; BISPO, D. L.; LIMA, A. D.; MELO, M. D.; KALIL-FILHO, R.; NICOLAU, J. C.; SALEMI, V. M.; MARANHAO, R. C.conferenceObject Lipid Core Nanoparticles as Vehicle of the Chemotherapeutic Docetaxel in the Treatment of Atherosclerosis Induced in Rabbits(2017) MENEGHINI, Bianca C.; TAVARES, Elaine R.; GUIDO, Maria C.; TAVONI, Tauany M.; MARQUES, Alyne F.; STEFANI, Helio A.; CHAGAS, Antonio C.; KALIL-FILHO, Roberto; MARANHAO, Raul C.- Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats(2017) MARANHAO, Raul C.; GUIDO, Maria C.; LIMA, Aline D. de; TAVARES, Elaine R.; MARQUES, Alyne F.; MELO, Marcelo D. Tavares de; NICOLAU, Jose C.; SALEMI, Vera Mc; KALIL-FILHO, RobertoPurpose: Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment. Materials and methods: Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery) or with LDE without drug (MI-controls). A sham-surgery group (n=12) was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy. Results: LDE-MTX treatment achieved a 40% improvement in left ventricular (LV) systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine bioavailability in the LV by increasing adenosine receptors and modulating adenosine catabolic enzymes. LDE-MTX increased the expression of myocardial vascular endothelium growth factor (VEGF) associated with adenosine release; this correlated not only with an increase in angiogenesis, but also with other parameters improved by LDE-MTX, suggesting that VEGF increase played an important role in the beneficial effects of LDE-MTX. Overall effects of commercial MTX were minor, and did not improve LV function or infarction size. Both treatments did not induce any toxicity. Conclusion: The remarkable improvement in heart function and reduction in infarction size achieved by LDE-MTX supports future clinical trials.
conferenceObject EFFECTS OF TREATMENT WITH METHOTREXATE ASSOCIATED TO LIPID NANOPARTICLES ON DIABETIC CARDIOMYOPATHY IN RATS(2017) MARANHAO, Raul Cavalcante; MARQUES, Alyne Franca; GUIDO, Maria Carolina; TAVARES, Elaine Rufo; BISPO, Deborah Lima; MELO, Marcelo Dantas Tavares de; SALEMI, Vera MariaconferenceObject Methotrexate reduces TNF-alpha and beta adrenergic receptor expression and improves left ventricle function in induced Takotsubo myocardiopathy in rats(2016) BISPO, D. L.; GUIDO, M. C.; MARQUES, A. F.; TAVARES, E. R.; MELO, M. D.; SALEMI, V. M.; MARANHAO, R. C.- The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas(2017) GUIDO, Maria C.; MARQUES, Alyne F.; TAVARES, Elaine R.; MELO, Marcelo D. Tavares de; SALEMI, Vera M. C.; MARANHAO, Raul C.Diabetic cardiomyopathy (DCM) is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN) and interstitial (INT) areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT) group and streptozotocin-induced diabetes (DM). After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV) were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.