Effects of diabetes mellitus on fibrin clot structure and mechanics in a model of acute neutrophil extracellular traps (Nets) formation
Judith J. de Vries (Erasmus MC)
Tamara Hoppenbrouwers (Erasmus MC, Wageningen University & Research)
Cristina Martinez-Torres (TU Delft - BN/Gijsje Koenderink Lab, Kavli institute of nanoscience Delft, AMOLF Institute for Atomic and Molecular Physics)
Rezin Majied (Erasmus MC)
Behiye Özcan (Erasmus MC)
Mandy van Hoek (Erasmus MC)
Frank W.G. Leebeek (Erasmus MC)
Dingeman C. Rijken (Erasmus MC)
Gijsje H. Koenderink (TU Delft - BN/Gijsje Koenderink Lab, Kavli institute of nanoscience Delft, AMOLF Institute for Atomic and Molecular Physics)
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Abstract
Subjects with diabetes mellitus (DM) have an increased risk of arterial thrombosis, to which changes in clot structure and mechanics may contribute. Another contributing factor might be an increased formation of neutrophil extracellular traps (NETs) in DM. NETs are mainly formed during the acute phase of disease and form a network within the fibrin matrix, thereby influencing clot properties. Previous research has shown separate effects of NETs and DM on clot properties, therefore our aim was to study how DM affects clot properties in a model resembling an acute phase of disease with NETs formation. Clots were prepared from citrated plasma from subjects with and without DM with the addition of NETs, induced in neutrophils by S. aureus bacteria or phorbol myristate acetate (PMA). Structural parameters were measured using scanning electron microscopy, mechanical properties using rheology, and sensitivity to lysis using a fluorescence-based fibrinolysis assay. Plasma clots from subjects with DM had significantly thicker fibers and fewer pores and branch points than clots from subjects without DM. In addition, fibrinolysis was significantly slower, while mechanical properties were similar between both groups. In conclusion, in a model of acute NETs formation, DM plasma shows prothrombotic effects on fibrin clots.
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