Apoptotic vascular endothelial cells become procoagulant
Apoptotic vascular endothelial cells become procoagulant
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DOI：
10.1182/blood.v89.7.2429
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发表时间：
1997-04-01
期刊：
影响因子：
20.3
通讯作者：
Harlan, JM
中科院分区：
文献类型：
--
作者：
Bombeli, T;Karsan, A;Harlan, JM
尽管未受干扰的内皮细胞提供了有效的抗凝特性，但暴露于炎症和致动脉粥样硬化刺激可迅速导致促凝血行为。由于最近的研究提供的证据表明，血管细胞的凋亡可能发生的条件下，如动脉粥样硬化和炎症，我们调查是否凋亡的内皮细胞可能有助于血栓前状态的发展。在这份报告中，它表明，无论是粘附和脱离凋亡的人脐静脉内皮细胞（HUVEC）成为促凝剂。细胞凋亡诱导星形孢菌素，一种非特异性蛋白激酶抑制剂，或通过培养悬浮液与血清剥夺。这两种方法得出了相似的结果。通过流式细胞术测定膜联蛋白V结合评估，经历细胞死亡的HUVEC通常表现出比DNA片段化更快的膜磷脂酰丝氨酸（PS）暴露。根据细胞凋亡的阶段，磷脂的这种重新分配被发现诱导增加的活性的内在tenase复合物的25%至60%。虽然凋亡细胞没有表现出抗原性或功能性组织因子（IF）活性，但当用脂多糖预活化时，TF促凝活性增加了50%至70%。在凋亡诱导后8小时，抗原性血栓调节蛋白、硫酸乙酰肝素和TF途径抑制剂分别降低约83%、80%和59%。这些组分的功能活性分别降低了约36%、52%和39%。此外，凋亡的HUVEC的存在导致凝血酶形成的显着增加，在抗凝的柠檬酸血浆。总之，凋亡HUVEC，无论是粘附或悬浮，成为促凝血PS的表达增加和抗凝膜成分的损失。(C)1997年，美国血液学会。
Whereas unperturbed endothelial cells provide potent anticoagulant properties, exposure to inflammatory and atherogenic stimuli can rapidly lead to a procoagulant behavior. Because recent studies provide evidence that apoptosis of vascular cells may occur under conditions such as atherosclerosis and inflammation, we investigated whether apoptotic endothelial cells may contribute to the development of a prothrombotic state. In this report, it is shown that both adherent and detached apoptotic human umbilical vein endothelial cells (HUVECs) become procoagulant. Apoptosis was induced by staurosporine, a nonspecific protein kinase inhibitor, or by culture in suspension with serum deprivation. Both methods resulted in similar findings. As assessed by flow cytometric determination of annexin V binding, HUVECs undergoing cell death exhibited typically a more rapid exposure of membrane phosphatidylserine (PS) than DNA fragmentation. Depending on the stage of apoptosis, this redistribution of phospholipids was found to induce an increase of the activity of the intrinsic tenase complex by 25% to 60%. Although apoptotic cells did not show antigenic or functional tissue factor (if) activity, when preactivated with lipopolysaccharide, TF procoagulant activity increased by 50% to 70%. At 8 hours after apoptosis induction, antigenic thrombomodulin, heparan sulfates, and TF pathway inhibitor decreased by about 83%, 80%, and 59%, respectively. The functional activity of these components was reduced by about 36%, 52%, and 39%, respectively. Moreover, the presence of apoptotic HUVECs led to a significant increase of thrombin formation in recalcified citrated plasma. In conclusion, apoptotic HUVECs, either adherent or in suspension, become procoagulant by increased expression of PS and the loss of anticoagulant membrane components. (C) 1997 by The American Society of Hematology.