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Farkas, Ádám Z.; Farkas, Veronika J.; Gubucz, István; Szabó, László; Bálint, Krisztián; Tenekedjiev, Kiril; Nagy, Anikó I.; Sótonyi, Péter; Hidi, László; Nagy, Zoltán; Szikora, István; Merkely, Béla; Kolev, Krasimir
Thrombosis research, 03/2019, Letnik: 175Journal Article
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. 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. 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. 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. •Neutrophil extracellular traps (NETs) modify the structure and stability of fibrin.•NET content of thrombi varies at different locations (brain, heart, peripheral arteries).•DNA and histones in thrombi correlate with age and systemic inflammatory markers.•The amount of fibrin is similar at all examined arterial locations.•Thicker fibrin fibers are formed in coronaries than in brain and peripheral arteries.
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