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Blood Coagul Fibrinolysis ; 18(7): 627-36, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17890950

RESUMO

Recent human studies reveal that hyperglycemia induces procoagulant and antifibrinolytic effects in blood that may contribute to a greater risk of arterial thrombosis, but the direct relationship between high blood glucose levels and thrombosis has not yet been investigated. We performed a number of experiments to clarify whether hyperglycemia was causally related to arterial thrombosis and whether the combined stimulus of hyperglycemia and inflammation would enhance the thrombotic effect. In a model of ferric-chloride-induced carotid artery thrombosis, hyperglycemia did not influence the time to occlusion in mice pretreated with streptozotocin, but the rate of thrombus formation was accelerated. This effect was associated with increased thrombin generation and could not be explained by changes in vessel-wall tissue factor activity. The prothrombotic effect of hyperglycemia was assessed in a separate experiment, showing that collagen/thrombin-induced platelet procoagulant activity was increased in hyperglycemic mice. The effect of inflammation was studied by injecting a low dose of endotoxin that caused a systemic inflammatory state after 24 h (increased plasma levels of tumor necrosis factor alpha, interleukin-6 and monocyte chemotactic protein 1 in diabetic and nondiabetic mice) associated with a mild delay in thrombus formation. This reduced rate of thrombus formation was attenuated by hyperglycemia. Together, these data establish a discrete but clear contribution of hyperglycemia in experimental arterial thrombosis.


Assuntos
Trombose das Artérias Carótidas/fisiopatologia , Endotoxinas/sangue , Fibrinolíticos/sangue , Hiperglicemia/fisiopatologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Trombose das Artérias Carótidas/induzido quimicamente , Trombose das Artérias Carótidas/prevenção & controle , Cloretos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Endotoxinas/farmacologia , Feminino , Compostos Férricos , Fibrinolíticos/farmacologia , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina , Trombina/efeitos dos fármacos , Tempo de Trombina/métodos , Tromboflebite/tratamento farmacológico , Tromboflebite/metabolismo
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