Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction.
Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction.
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DOI：
10.1093/eurheartj/ehv007
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发表时间：
2015-06-07
影响因子：
39.3
通讯作者：
Ritis K
中科院分区：
文献类型：
--
作者：
Stakos DA;Kambas K;Konstantinidis T;Mitroulis I;Apostolidou E;Arelaki S;Tsironidou V;Giatromanolaki A;Skendros P;Konstantinides S;Ritis K
中性粒细胞通过NET结构参与STEMI中冠状动脉梗死的病理生理学。由凝血酶激活的血小板是NET形成所必需的，而NET支架的完整性有助于NET结合TF的功能。NET形成的阻断或NET介导的TF信号传导的局部中和构成候选治疗靶点。中性粒细胞胞外陷阱（NETs）是由活化的多形核中性粒细胞（PMNs）释放的染色质纤维，并由具有各种特性的颗粒蛋白装饰。几条证据表明NET与血栓形成有关。NET在人类动脉粥样硬化血栓形成过程中的功能意义和体内相关性至今尚未得到解决。对18例ST段抬高型急性心肌梗死（STEMI）患者在直接经皮血运重建术中选择性采集梗死相关冠状动脉（伊拉）和非IRA的血栓物质和周围血液。从伊拉分离的血栓含有组织因子（TF）修饰的中性粒细胞和中性粒细胞。虽然TF在STEMI患者的循环PMN中细胞内表达，但从斑块破裂部位获得的NET特异性暴露了活性TF。用DNase I处理NET结构废除了TF功能测量。在体外处理对照PMNs与血浆从伊拉和非IRA获得进一步显示，诱导TF的细胞内上调，但不是NET的形成。第二步包括中性粒细胞和凝血酶激活的血小板之间的相互作用，需要NET生成和随后的TF曝光。急性ST段抬高型心肌梗死（STEMI）时血小板与中性粒细胞在斑块破裂部位的相互作用导致局部NET形成和活性TF的释放。NETs代表了动脉粥样硬化血栓形成过程中中性粒细胞释放血栓形成信号的机制，这一观点可能提供新的治疗靶点。
Neutrophils are involved in the pathophysiology of infracted coronary arteries in STEMI via NET structures. Platelets, activated by thrombin, are required for NET formation, while the integrity of NET scaffold contributes to the functionality of NET-bound TF. The blockage of NET formation or local neutralization of NET-mediated TF signalling constitutes candidate therapeutic targets. Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now. Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST-segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure. The interaction of thrombin-activated platelets with PMNs at the site of plaque rupture during acute STEMI results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets.
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DOI：
10.1084/jem.20112322
发表时间：
2012-04-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
von Brühl ML;Stark K;Steinhart A;Chandraratne S;Konrad I;Lorenz M;Khandoga A;Tirniceriu A;Coletti R;Köllnberger M;Byrne RA;Laitinen I;Walch A;Brill A;Pfeiler S;Manukyan D;Braun S;Lange P;Riegger J;Ware J;Eckart A;Haidari S;Rudelius M;Schulz C;Echtler K;Brinkmann V;Schwaiger M;Preissner KT;Wagner DD;Mackman N;Engelmann B;Massberg S
通讯作者：
Massberg S
影响因子：
7.3
作者：
Kambas K;Mitroulis I;Ritis K
通讯作者：
Ritis K
影响因子：
10.4
作者：
Maugeri, N.;Campana, L.;Manfredi, A. A.
通讯作者：
Manfredi, A. A.
影响因子：
15.9
作者：
Caudrillier, Axelle;Kessenbrock, Kai;Looney, Mark R.
通讯作者：
Looney, Mark R.
影响因子：
10.8
作者：
Szotowski, Bjoern;Antoniak, Silvio;Rauch, Ursula
通讯作者：
Rauch, Ursula