Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques -: A role for apoptosis in plaque thrombogenicity
Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques -: A role for apoptosis in plaque thrombogenicity
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DOI：
10.1161/01.cir.99.3.348
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发表时间：
1999-01-26
期刊：
影响因子：
37.8
通讯作者：
Tedgui, A
中科院分区：
文献类型：
--
作者：
Mallat, Z;Hugel, B;Tedgui, A
背景--细胞凋亡在人类动脉粥样硬化中的具体作用尚不清楚。在凋亡细胞死亡过程中，暴露于细胞表面的磷脂酰丝氨酸赋予高度依赖于组织因子(TF)的促凝血活性。方法和结果：在本研究中，我们研究了凋亡细胞死亡在促进斑块血栓形成中的作用。应用免疫组织化学技术检测了16例人动脉粥样硬化斑块组织中TF的表达及其与细胞凋亡的关系。分析了6个人动脉粥样硬化斑块和3个动脉壁下的提取液中脱落膜凋亡微粒的存在。这些微粒被膜联蛋白V捕获，并通过凝血酶原酶试验根据其磷脂含量估计它们的量。通过测定提取物中总的和微粒依赖的转铁蛋白活性，进一步评估了微粒的血栓形成潜能。被特定抗体捕获后，确定微粒的细胞来源。我们能够在靠近凋亡细胞和碎片的斑块中检测到显著的TF表达，这表明TF与凋亡细胞表面之间存在潜在的相互作用。在动脉粥样硬化斑块提取液中检测到高水平的脱落膜凋亡微粒，而在动脉壁下未检测到(29.5+/-3.7nmol/L磷脂酰丝氨酸当量对1.3+/-0.4nmol/L，P
Background-The specific role of apoptosis in human atherosclerosis remains unknown. During apoptotic cell death, phosphatidylserine exposure on the cell surface confers a high tissue-factor (TF)-dependent procoagulant activity.Methods and Results-In this study, we examined the role of apoptotic cell death in the promotion of plaque thrombogenicity. TF expression and its relation to apoptosis was analyzed in 16 human atherosclerotic plaques by the use of immunohistochemical techniques. The presence of shed membrane apoptotic microparticles was analyzed in extracts from 6 human atherosclerotic plaques and 3 underlying arterial walls. The microparticles were captured by annexin V and their amounts estimated with respect to their phospholipid content by use of a prothrombinase assay. The prothrombogenic potential of the microparticles was further assessed by the measurement of total and microparticle-dependent TF activity in the extracts. The cell origin of the microparticles was determined after capture by specific antibodies. We were able to detect marked TF expression in the plaques in close proximity to apoptotic cells and debris, suggesting a potential interaction between TF and the apoptotic cell surfaces. High levels of shed membrane apoptotic microparticles were detected in extracts from atherosclerotic plaques but not in the underlying arterial walls (29.5+/-3.7 nmol/L phosphatidylserine equivalent versus 1.3+/-0.4 nmol/L, respectively, P