Background: Extracellular traps formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils.
View Article and Find Full Text PDFJACC Basic Transl Sci
November 2023
In addition to its potent antiplatelet activity, ticagrelor possesses antibacterial properties against gram-positive bacteria. We wondered whether the typical clinical dosage of ticagrelor could prevent the development of infective endocarditis caused by highly virulent . Ticagrelor prevented vegetation formation in a mouse model of inflammation-induced endocarditis.
View Article and Find Full Text PDFObjectives: We aimed at determining whether specific S. aureus strains cause infective endocarditis (IE) in the course of Staphylococcus aureus bacteraemia (SAB).
Methods: A genome-wide association study (GWAS) including 924 S.
Arterioscler Thromb Vasc Biol
February 2023
Background: Infective endocarditis (IE) is characterized by an infected thrombus at the heart valves. How bacteria bypass the immune system and cause these thrombi remains unclear. Neutrophils releasing NETs (neutrophil extracellular traps) lie at this interface between host defense and coagulation.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
March 2022
Over the past 10 years, neutrophil extracellular traps (NETs) have become widely accepted as an integral player in immunothrombosis, due to their complex interplay with both pathogens and components of the coagulation system. While the release of NETs is an attempt by neutrophils to trap pathogens and constrain infections, NETs can have bystander effects on the host by inducing uncontrolled thrombosis, inflammation, and tissue damage. From an evolutionary perspective, pathogens have adapted to bypass the host innate immune response.
View Article and Find Full Text PDFEnergy-coupling factor type transporters (ECF) represent trace nutrient acquisition systems. Substrate binding components of ECF-transporters are membrane proteins with extraordinary affinity, allowing them to scavenge trace amounts of ligand. A number of molecules have been described as substrates of ECF-transporters, but an involvement in iron-acquisition is unknown.
View Article and Find Full Text PDFInfective endocarditis is a life-threatening and enigmatic disease with a mortality of 30% and a pathophysiology that is poorly understood. However, at its core, an endocarditis lesion is mainly a fibrin and platelet blood clot infested with bacteria, clinging at the cardiac valves. Infective endocarditis therefore serves as a paradigm of immunothrombosis gone wrong.
View Article and Find Full Text PDFBackground: Previous clinical evidence correlates levels of von Willebrand factor (VWF) and its cleaving protease ADAMTS13 with outcome in septic patients. No previous studies addressed if VWF and ADAMTS13 affected the outcome of Staphylococcus aureus sepsis.
Objectives: We studied the role of VWF and ADAMTS13 in S.
Aims: The pathogenesis of endocarditis is not well understood resulting in unsuccessful attempts at prevention. Clinical observations suggest that Staphylococcus aureus infects either damaged or inflamed heart valves. Using a newly developed endocarditis mouse model, we therefore studied the initial adhesion of S.
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