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Markers of neutrophil extracellular traps are associated with adverse clinical outcome in stable coronary artery disease

Published on May 1, 2018in European Journal of Preventive Cardiology5.64
· DOI :10.1177/2047487318760618
Miriam Sjåstad Langseth1
Estimated H-index: 1
(University of Oslo),
Trine B. Opstad10
Estimated H-index: 10
(University of Oslo)
+ 5 AuthorsRagnhild Helseth3
Estimated H-index: 3
(University of Oslo)
Abstract
BackgroundNeutrophil extracellular traps, comprising chromatin and granule proteins, have been implicated in atherothrombosis.Design and methodsWe investigated whether the circulating neutrophil extracellular traps markers, double-stranded DNA and myeloperoxidase-DNA were associated with clinical outcome and hypercoagulability in patients with stable coronary artery disease. Patients with angiographically verified stable coronary artery disease (n = 1001) were included. Follow-up was 2 years, recording 106 clinical endpoints (unstable angina, non-haemorrhagic stroke, myocardial infarction or death). Serum collected at baseline was used to determine double-stranded DNA and myeloperoxidase-DNA levels.ResultsThe neutrophil extracellular traps markers were weakly intercorrelated (r = 0.103, P = 0.001). Patients with the highest quartile of double-stranded DNA had weakly but significantly elevated hypercoagulability markers (prothrombin fragment 1+2, D-dimer, free and total tissue factor pathway inhibitor (P <...
  • References (37)
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References37
Newest
#1Juana VallésH-Index: 18
#2Aida LagoH-Index: 19
Last. Antonio MoscardóH-Index: 11
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Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with...
20 CitationsSource
#1Denis Noubouossie (UNC: University of North Carolina at Chapel Hill)H-Index: 4
#2Matthew F. Whelihan (UNC: University of North Carolina at Chapel Hill)H-Index: 5
Last. Nigel S. Key (UNC: University of North Carolina at Chapel Hill)H-Index: 57
view all 7 authors...
NETosis is a physiological process in which neutrophils release their nuclear material in the form of neutrophil extracellular traps (NETs). NETs have been reported to directly promote thrombosis in animal models. Although the effects of purified NET components including DNA, histone proteins and neutrophil enzymes on coagulation have been characterized, the mechanism by which intact NETs promote thrombosis is largely unknown. In this study, human neutrophils were stimulated to produce NETs in p...
51 CitationsSource
#1Yvonne Döring (LMU: Ludwig Maximilian University of Munich)H-Index: 23
#2Oliver SoehnleinH-Index: 51
Last. Christian WeberH-Index: 105
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Neutrophil extracellular traps expelled from suicidal neutrophils comprise a complex structure of nuclear chromatin and proteins of nuclear, granular, and cytosolic origin. These net-like structures have also been detected in atherosclerotic lesions and arterial thrombi in humans and mice. Functionally, neutrophil extracellular traps have been shown to induce activation of endothelial cells, antigen-presenting cells, and platelets, resulting in a proinflammatory immune response. Overall, this su...
65 CitationsSource
#1Ava Hosseinzadeh (Umeå University)H-Index: 6
#2Paul R. Thompson (UMMS: University of Massachusetts Medical School)H-Index: 50
Last. Constantin F. Urban (Umeå University)H-Index: 23
view all 4 authors...
NETs serve to ensnare and kill microbial pathogens. However, NETs can at the same time contribute to tissue damage and excessive inflammation. Nicotine is a major toxic agent and has been associate ...
38 CitationsSource
#1Quinte Braster (LMU: Ludwig Maximilian University of Munich)H-Index: 3
#2Carlos Silvestre Roig (LMU: Ludwig Maximilian University of Munich)H-Index: 1
Last. Oliver Soehnlein (LMU: Ludwig Maximilian University of Munich)H-Index: 51
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Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs ma...
6 CitationsSource
#1Sakiko Masuda (Hokkaido University)H-Index: 7
#2Daigo Nakazawa (Hokkaido University)H-Index: 15
Last. Akihiro Ishizu (Hokkaido University)H-Index: 21
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Abstract More than 10 years have passed since the discovery of neutrophil extracellular traps (NETs) in 2004. NETs are extracellular web-like DNA decorated with antimicrobial proteins, which are released from activated neutrophils. The state of neutrophils with NET formation is called NETosis. It has been realized that NETosis includes suicidal NETosis and vital NETosis. The former state means cell death of neutrophils, whereas the latter state preserves living neutrophilic functions. Although b...
39 CitationsSource
#1Quinte BrasterH-Index: 3
Last. Oliver SoehnleinH-Index: 51
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Cathelicidin regulates myeloid cell accumulation in adipose tissue and promotes insulin resistance during obesity -
3 CitationsSource
#1Travis J. Gould (McMaster University)H-Index: 8
#2Trang T. Vu (McMaster University)H-Index: 8
Last. Patricia C. Liaw (McMaster University)H-Index: 29
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Objectives—Sepsis is characterized by systemic activation of inflammation and coagulation in response to infection. In sepsis, activated neutrophils extrude neutrophil extracellular traps composed of cell-free DNA (CFDNA) that not only trap pathogens but also provide a stimulus for clot formation. Although the effect of CFDNA on coagulation has been extensively studied, much less is known about the impact of CFDNA on fibrinolysis. To address this, we (1) investigated the relationship between CFD...
42 CitationsSource
#1Dimitrios Stakos (DUTH: Democritus University of Thrace)H-Index: 23
#2Konstantinos Kambas (DUTH: Democritus University of Thrace)H-Index: 20
Last. Konstantinos Ritis (DUTH: Democritus University of Thrace)H-Index: 30
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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 (I...
115 CitationsSource
#1Thibaut Quillard (University of Nantes)H-Index: 20
#2Haniel Alves Araújo (Brigham and Women's Hospital)H-Index: 2
Last. Peter Libby (Brigham and Women's Hospital)H-Index: 187
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Aims Superficial erosion of atheromata causes many acute coronary syndromes, but arises from unknown mechanisms. This study tested the hypothesis that Toll-like receptor-2 (TLR2) activation contributes to endothelial apoptosis and denudation and thus contributes to the pathogenesis of superficial erosion. Methods and results Toll-like receptor-2 and neutrophils localized at sites of superficially eroded human plaques. In vitro , TLR2 ligands (including hyaluronan, a matrix macromolecule abundant...
90 CitationsSource
Cited By6
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#1Shida Yousefi (University of Bern)H-Index: 44
#2Dagmar Simon (University of Bern)H-Index: 37
Last. Hans-Uwe Simon (University of Bern)H-Index: 85
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Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological condition...
Source
#1Yvonne Döring (LMU: Ludwig Maximilian University of Munich)H-Index: 23
#2Peter Libby (Brigham and Women's Hospital)H-Index: 187
Last. Oliver Soehnlein (LMU: Ludwig Maximilian University of Munich)H-Index: 51
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Neutrophil extracellular traps (NETs) have recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries and propagate and amplify the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thr...
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#1Karsten E. Kluge (University of Oslo)
#2Miriam Sjåstad Langseth (University of Oslo)H-Index: 1
Last. Ragnhild Helseth (Oslo University Hospital)H-Index: 3
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Source
#1Aldo BonaventuraH-Index: 17
Last. Fabrizio MontecuccoH-Index: 38
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Neutrophil extracellular traps (NETs) are formed by decondensed chromatin, histones, and neutrophil granular proteins and have a role in entrapping microbial pathogens. NETs, however, have pro-thrombotic properties by stimulating fibrin deposition, and increased NET levels correlate with larger infarct size and predict major adverse cardiovascular (CV) events. NETs have been involved also in the pathogenesis of diabetes, as high glucose levels were found to induce NETosis. Accordingly, NETs have...
Source
#1Ragnhild Helseth (Oslo University Hospital)H-Index: 3
#1R Helseth (Oslo University Hospital)H-Index: 1
Last. Ingebjørg Seljeflot (University of Oslo)H-Index: 44
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Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were me...
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Neutrophil extracellular traps (NETs) have recently been identified as mediators in atherothrombosis. Although NETosis in general has been suggested to be glucose dependent, the transferability to patients with acute ST-elevation myocardial infarction (STEMI) is unclear. We assessed whether the NETs markers double-stranded deoxyribonucleid acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) associated with plasma glucose and the glucometabolic status in the acute phase and 3 months after a STEMI. We ...
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Abstract Myeloperoxidase (MPO) is a member of the superfamily of heme peroxidases that is mainly expressed in neutrophils and monocytes. MPO-derived reactive species play a key role in neutrophil antimicrobial activity and human defense against various pathogens primarily by participating in phagocytosis. Elevated MPO levels in circulation are associated with inflammation and increased oxidative stress. Multiple lines of evidence suggest an association between MPO and cardiovascular disease (CVD...
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Background Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at three time-points, and examined their association with microbial aetiology and adverse clinical outcomes in CAP. Methods Blood samples were obtained at hos...
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#1Kathryn E. Hally (Wellington Management Company)H-Index: 3
#2Kirsty M. Danielson (Wellington Management Company)
Last. Peter D. Larsen (Wellington Management Company)H-Index: 26
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Purpose of Review Coronary artery disease (CAD) continues to be a major contributor to death and disability worldwide. Emerging biomarkers that are linked to CAD pathophysiology have the potential to phenotype CAD severity and identify individuals at high risk for experiencing future CAD events. This review discusses the utility of emergent biomarkers for CAD risk prediction.
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#1Aaron P. Kithcart (Brigham and Women's Hospital)H-Index: 9
#2Peter Libby (Brigham and Women's Hospital)H-Index: 187
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