Ádám Z Farkas1, Veronika J Farkas1, István Gubucz2, László Szabó3, Krisztián Bálint1, Kiril Tenekedjiev4, Anikó I Nagy5, Péter Sótonyi5, László Hidi5, Zoltán Nagy2, István Szikora2, Béla Merkely5, Krasimir Kolev6. 1. Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary. 2. National Institute of Clinical Neurosciences, Budapest, Hungary. 3. Department of Functional and Structural Materials, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. 4. Department of Information Technology, Nikola Vaptsarov Naval Academy, Varna, Bulgaria; Australian Maritime College, University of Tasmania, Launceston, Australia. 5. Heart and Vascular Center, Semmelweis University, Budapest, Hungary. 6. Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary. Electronic address: Krasimir.Kolev@eok.sote.hu.
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.
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.
Authors: Brandon Bautista-Becerril; Rebeca Campi-Caballero; Samuel Sevilla-Fuentes; Laura M Hernández-Regino; Alejandro Hanono; Al Flores-Bustamante; Julieta González-Flores; Carlos A García-Ávila; Arnoldo Aquino-Gálvez; Manuel Castillejos-López; Armida Juárez-Cisneros; Angel Camarena Journal: Biomolecules Date: 2021-05-06
Authors: László Hidi; Erzsébet Komorowicz; Gergely Imre Kovács; Zoltán Szeberin; Dávid Garbaisz; Natalia Nikolova; Kiril Tenekedjiev; László Szabó; Krasimir Kolev; Péter Sótonyi Journal: PLoS One Date: 2021-07-22 Impact factor: 3.240
Authors: Svitlana Demyanets; Stefan Stojkovic; Lisa-Marie Mauracher; Christoph W Kopp; Johann Wojta; Johannes Thaler; Simon Panzer; Thomas Gremmel Journal: J Clin Med Date: 2020-01-22 Impact factor: 4.241