Apoptotic vascular endothelial cells become procoagulant

作者: Thomas Bombeli , Aly Karsan , Jonathan F. Tait , John M. Harlan

DOI: 10.1182/BLOOD.V89.7.2429

关键词:

摘要: Whereas unperturbed endothelial cells provide potent anticoagulant properties, exposure to inflammatory and atherogenic stimuli can rapidly lead a procoagulant behavior. Because recent studies evidence that apoptosis of vascular may occur under conditions such as atherosclerosis inflammation, we investigated whether apoptotic contribute the development prothrombotic state. In this report, it is shown both adherent detached human umbilical vein (HUVECs) become procoagulant. Apoptosis was induced by staurosporine, nonspecific protein kinase inhibitor, or culture in suspension with serum deprivation. Both methods resulted similar findings. As assessed flow cytometric determination annexin V binding, HUVECs undergoing cell death exhibited typically more rapid membrane phosphatidylserine (PS) than DNA fragmentation. Depending on stage apoptosis, redistribution phospholipids found induce an increase activity intrinsic tenase complex 25% 60%. Although did not show antigenic functional tissue factor (TF) activity, when preactivated lipopolysaccharide, TF increased 50% 70%. At 8 hours after induction, thrombomodulin, heparan sulfates, pathway inhibitor decreased about 83%, 80%, 59%, respectively. The these components reduced 36%, 52%, 39%, Moreover, presence led significant thrombin formation recalcified citrated plasma. conclusion, HUVECs, either suspension, expression PS loss components.

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