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

Citation

Farkas, AZ and Farkas, VJ and Gubucz, I and Szabo, L and Balint, K and Tenekedjiev, K and Nagy, AI and Sotonyi, P and Hidi, L and Nagy, Z and Szikora, I and Merkely, B and Kolev, K, Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases, Thrombosis Research, 175 pp. 46-52. ISSN 0049-3848 (2019) [Refereed Article]


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Copyright Statement

Copyright 2019 Elsevier Ltd.

DOI: doi:10.1016/j.thromres.2019.01.006

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.

Item Details

Item Type:Refereed Article
Keywords:fibrin, myocardial infarction, stroke, peripheral artery disease, neutrophil extracellular traps
Research Division:Mathematical Sciences
Research Group:Numerical and Computational Mathematics
Research Field:Numerical Analysis
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Information and Computing Sciences
UTAS Author:Tenekedjiev, K (Professor Kiril Tenekedjiev)
ID Code:130228
Year Published:2019
Deposited By:AMC Governance Office
Deposited On:2019-01-16
Last Modified:2019-06-04
Downloads:0

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