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Lina Badimon, Gemma Vilahur, Neutrophil extracellular traps: a new source of tissue factor in atherothrombosis, European Heart Journal, Volume 36, Issue 22, 7 June 2015, Pages 1364–1366, https://doi.org/10.1093/eurheartj/ehv105
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This editorial refers to ‘Expression of functional tissue factor by neutrophil extracellular traps in the culprit artery of acute myocardial infarction’†, by D.A. Stakos et al., on page 1405.
Atherosclerotic cardiovascular diseases are still major causes of morbidity and mortality worldwide. Sudden rupture of vulnerable atherosclerotic plaques expose to the flowing blood prothrombotic molecules that trigger platelet aggregates that grow in association with an increase in fibrin deposition and further entrapment of inflammatory and red blood cells.1 The resulting thrombus may lead to blood flow cessation and subsequent acute ST-elevation myocardial infarction (STEMI).2 Thrombus aspiration has offered a unique opportunity to characterize antemortem the culprit coronary thrombus. In this regard, within the last years several studies in coronary thrombectomy specimens extracted from occluded arteries have provided insights as to thrombus composition, reporting that platelets, erythrocytes, and activated neutrophils are major contributors of arterial thrombosis after plaque rupture.3–6
Neutrophils are critical components of the innate immune system launching the first line of host defence against invading microorganisms. Seminal work by Brinkman and colleagues in 20047 revealed that, in addition to the well-established mechanism of phagocytosis, activated neutrophils fight microbes through the release of web-like filamentous structures of decondensed chromatin (so-called neutrophil extracellular traps, NETs). NETs are composed of DNA and histones, and harbour granular components [such as myeloperoxidase (MPO), neutrophil elastase, and cathepsin G] that exert antimicrobial properties.8 During the last years, however, several in vivo models of thrombosis have described a critical role for neutrophils in linking sepsis and deep venous thrombosis through release of NETs.9In vitro data have supported the ability of NETs to stimulate the activation of the coagulation cascade (both the extrinsic and the intrinsic pathway) and platelet adhesion. As such, isolated nucleic acids have been shown to activate the coagulation pathway by binding both factor XII and XI; purified histones have been shown to impair thrombomodulin-dependent protein C activation enhancing plasma thrombin generation; and neutrophil serine proteases have been shown to inactivate tissue factor (TF) pathway inhibitor through cleavage, with an ensuing increase in factor Xa procoagulant activity.10 On the other hand, DNA and histones have been shown to interact and trap platelets most probably via electrostatic interactions or via Toll-like receptors (TLRs).
