4.7 Article

Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction

Journal

EUROPEAN HEART JOURNAL
Volume 36, Issue 22, Pages 1405-1414

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehv007

Keywords

Myocardial infarction; Thrombosis; Inflammation; Neutrophil extracellular traps; Tissue factor

Funding

  1. Hellenic Ministry of Education
  2. General Secretariat for Research and Technology [898]
  3. Hellenic Cardiologic Society
  4. National and European Union funds from the 'Operational Program Education and Life Long Learning' [379 527]
  5. German Federal Ministry of Education and Research (BMBF) [01EO1003]
  6. Hellenic Cardiological Society

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Aims 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. Methods and results 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. Conclusion The interaction of thrombin-activated platelets with PMN sat 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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