Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases

Ádám Z. Farkas, Veronika J. Farkas, István Gubucz, László Szabó, Krisztián Bálint, Kiril Tenekedjiev, Anikó I. Nagy, P. Sótonyi, László Hidi, Zoltán Nagy, I. Szikora, B. Merkely, K. Kolev

Research output: Contribution to journalArticle

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Abstract

Introduction: The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data. Patients and methods: Thrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters. Results: DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients’ age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers. Conclusions: The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases.

Original languageEnglish
Pages (from-to)46-52
Number of pages7
JournalThrombosis Research
Volume175
DOIs
Publication statusPublished - Mar 1 2019

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Thrombosis
Peripheral Arterial Disease
Fibrin
Histones
Stroke
DNA
Therapeutics
Blood Platelets
Extracellular Traps
Electron Scanning Microscopy
Coronary Artery Disease
Neutrophils
Antigens

Keywords

  • Fibrin
  • Myocardial infarction
  • Neutrophil extracellular traps
  • Peripheral artery disease
  • Stroke

ASJC Scopus subject areas

  • Hematology

Cite this

Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases. / Farkas, Ádám Z.; Farkas, Veronika J.; Gubucz, István; Szabó, László; Bálint, Krisztián; Tenekedjiev, Kiril; Nagy, Anikó I.; Sótonyi, P.; Hidi, László; Nagy, Zoltán; Szikora, I.; Merkely, B.; Kolev, K.

In: Thrombosis Research, Vol. 175, 01.03.2019, p. 46-52.

Research output: Contribution to journalArticle

Farkas, Ádám Z. ; Farkas, Veronika J. ; Gubucz, István ; Szabó, László ; Bálint, Krisztián ; Tenekedjiev, Kiril ; Nagy, Anikó I. ; Sótonyi, P. ; Hidi, László ; Nagy, Zoltán ; Szikora, I. ; Merkely, B. ; Kolev, K. / Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases. In: Thrombosis Research. 2019 ; Vol. 175. pp. 46-52.
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abstract = "Introduction: The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data. Patients and methods: Thrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters. Results: DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients’ age. The median platelet content was lower in PAD (2.2{\%}) than in either AIS (3.9{\%}) or CAD (3.1{\%}) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers. Conclusions: The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases.",
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AU - Farkas, Ádám Z.

AU - Farkas, Veronika J.

AU - Gubucz, István

AU - Szabó, László

AU - Bálint, Krisztián

AU - Tenekedjiev, Kiril

AU - Nagy, Anikó I.

AU - Sótonyi, P.

AU - Hidi, László

AU - Nagy, Zoltán

AU - Szikora, I.

AU - Merkely, B.

AU - Kolev, K.

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N2 - Introduction: The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data. Patients and methods: Thrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters. Results: DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients’ age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers. Conclusions: The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases.

AB - Introduction: The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data. Patients and methods: Thrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters. Results: DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients’ age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers. Conclusions: The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases.

KW - Fibrin

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