Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques - Effects of tissue factor pathway inhibitor on plaque thrombogenicity under flow conditions
Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques - Effects of tissue factor pathway inhibitor on plaque thrombogenicity under flow conditions
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DOI：
10.1161/01.cir.99.14.1780
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发表时间：
1999-04-13
期刊：
影响因子：
37.8
通讯作者：
Badimon, L
中科院分区：
文献类型：
--
作者：
Badimon, JJ;Lettino, M;Badimon, L
斑块破裂和随后的血栓形成导致急性冠状动脉综合征和动脉粥样硬化疾病的进展。组织因子（TF）似乎介导斑块血栓形成。组织因子途径抑制物（TFPI）是TF的主要生理抑制物。本研究分析了TF对破坏人动脉粥样硬化斑块的血栓形成的作用及其特异性inhibit 1 n.Methods和Results-Human动脉粥样硬化和正常动脉段暴露于肝素化的血液在流动条件下建模中等冠状动脉狭窄的Badimon灌注室。通过减少放射性标记的血小板和纤维蛋白原的沉积和灌注动脉的免疫组织化学分析来评估斑块TF的特异性抑制的抗血栓形成作用。重组TFPI和抗人TF的多克隆抗体均可抑制TF活性。人类富含脂质的斑块比不太先进的动脉粥样硬化斑块更血栓形成。特异性抑制TF活性可降低斑块血栓形成，抑制血小板和纤维蛋白原沉积（580对194血小板x10（6）/cm（2）; P
Background-Plaque disruption and subsequent thrombus formation lead to acute coronary syndromes and progression of atherosclerotic disease. Tissue factor (TF) appears to mediate plaque thrombogenicity. Tissue factor pathway inhibitor (TFPI) is the major physiological inhibitor of TF. This study analyzes the role of TF on thrombogenicity of disrupted human atherosclerotic plaques and the therapeutic possibilities of its specific inhibition.Methods and Results-Human atherosclerotic and normal arterial segments were exposed to heparinized blood at flow conditions modeling medium-grade coronary stenosis in the Badimon perfusion chamber. The antithrombotic effects of the specific inhibition of plaque TF was assessed by reduction in the deposition of radiolabeled platelets and Fibrin(ogen) and immunohistochemical analysis of perfused arteries. TF activity was inhibited by both recombinant TFPI and a polyclonal antibody against human TF. Human lipid-rich plaques were more thrombogenic than less advanced atherosclerotic plaques. Specific inhibition of TF activity reduced plaque thrombogenicity, inhibiting both platelet and fibrin(ogen) deposition (580 versus 194 plateletsx10(6)/cm(2); P