VERA MARIA CURY SALEMI
Projetos de Pesquisa
Unidades Organizacionais
LIM/65, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
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 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 Maria- 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.