RESUMO
BACKGROUND: Obesity and its complications lead to vascular injury, atherosclerosis, diabetes and pathological angiogenesis. One of the models to study the obesity and its entanglements is the New Zealand Obese mice model. Aim of this study was to check the effect of high fat diet on changes in biochemical parameters as well as on process of angiogenesis in NZO mice. METHODS: NZO mice were fed with standard (ST) or high fat (HF) diet for seven weeks. Body weight and serum biochemical parameters were monitored. The PECAM1 positive vessel-like structures immunostaining, as well as the gene expression of the matrigel penetrating cells by microarray (confirmed by real-time PCR method) were analyzed. RESULTS: Mice fed with HF diet developed obesity. Number of newly created vessels with lumen was correlated with hyperglycemia and animal weight gain. The number of PECAM1 positive cells in matrigel tended to increase during HF diet. Microarray results revealed changes in gene expression (activation of the oxidative stress and insulin resistance, inhibition of apoptosis and cell differentiation), however without markers of endothelial cell network maturation. CONCLUSION: Observed changes in the NZO mice on HF diet argue for the hyperglycemia related activation of angiogenesis, leading to the formation of pathological, immature network.
Assuntos
Neovascularização Patológica/etiologia , Obesidade/patologia , Animais , Biomarcadores/sangue , Peso Corporal , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Hiperglicemia/fisiopatologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos , Obesidade/complicações , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análiseRESUMO
Leptin is prompt to drive angiogenesis, effecting proper vascularisation. Tissue remodeling (including adipose organ) is associated with the angiogenic response. The aim of this study was to investigate the effect of hyperleptinemia on angiogenesis in subcutaneous (s.c.) in vivo matrigel model in mice on a high fat (HF) diet. HF promoted adipose tissue accumulation and biochemical changes resembling metabolic syndrome. However, the impact of this dietary treatment on angiogenesis, measured in s.c. matrigel model was not significant. Changes in leptin concentration were not accompanied by significant angiogenic response. This lack of leptin activity and impaired signal transduction at the molecular level suggests malfunction of the leptin receptor in NZO mice.
RESUMO
Neutropenia is the most often side effect during antineoplastic treatment. In this article current recommendations for clinical applications of granulocyte and granulocyto-macrophage hematopoietic factors and possibility of protection of neutropenia, and its serious complications in pediatric oncology are presented.
Assuntos
Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Agranulocitose/induzido quimicamente , Agranulocitose/prevenção & controle , Criança , Filgrastim , Humanos , Neoplasias/complicações , Neutropenia/prevenção & controle , Proteínas Recombinantes/uso terapêuticoRESUMO
OBJECTIVES: Endothelial cells and their progenitors play an important role in angiogenesis that is essential for organogenesis and tissue remodelling, as well as for inflammatory responses and carcinogenesis in all periods of life. In the present study, the authors concentrated on the direct effect of beta-carotene (BC) on human umbilical cord-originated endothelial progenitor cells and human umbilical vein endothelial cells. METHODS: BC uptake was measured using high-performance liquid chromatography. The effect on cell proliferation was measured based on bromodeoxyuridine incorporation. Chemotaxis was performed in a Boyden chamber. The influence on tubular-like structure formation was investigated using a three-dimensional assay in Matrigel (Becton Dickinson, USA) both in an in vitro and in vivo model. Changes in gene expression were analyzed using the microarray hybridization method. Quantitative gene expression was estimated using the real-time polymerase chain reaction method. RESULTS: It was shown that BC, in the physiological range of concentrations found in human blood, is a potent activator of chemotaxis of endothelial cells. Microarray data analysis revealed that the genes involved in cell-cell and cell-matrix adhesion, matrix reorganization and activation of chemotaxis were the most affected by BC genes in human umbilical vein endothelial cells and endothelial progenitor cells. These results were also confirmed in an in vivo angiogenesis model. CONCLUSION: BC, in the range of physiological concentrations, stimulates early steps of angiogenic activity of endothelial cells by activation of cellular migration, as well as by matrix reorganization and a decrease in cellular adhesion.