A5047951861- Blood Coagulation and Thrombosis Mechanisms
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Platelet Disorders and Treatments
- Sepsis Diagnosis and Treatment
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- Venomous Animal Envenomation and Studies
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Atherosclerosis and Cardiovascular Diseases
- COVID-19 Clinical Research Studies
- Complement system in diseases
- Protease and Inhibitor Mechanisms
- NF-κB Signaling Pathways
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Venous Thromboembolism Diagnosis and Management
- Phagocytosis and Immune Regulation
- Protein Structure and Dynamics
- Chemokine receptors and signaling
- Vitamin K Research Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Heparin-Induced Thrombocytopenia and Thrombosis
Maastricht University
2016-2025
Amsterdam University Medical Centers
2018-2024
University of Amsterdam
1994-2024
KU Leuven
2019
GTx (United States)
2019
Amsterdam UMC Location University of Amsterdam
1994-2016
Novem (Netherlands)
2016
Leiden University Medical Center
2013
Yale University
2013
Children's Hospital of Philadelphia
2013
Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression. The authors recently identified small molecule inhibitors that block interaction between CD40 and tumor necrosis factor receptor-associated (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity.This study evaluates potential of TRAF-STOP treatment atherosclerosis.The effects TRAF-STOPs on atherosclerosis were investigated...
Background: Acute infection is a well-established risk factor of cardiovascular inflammation increasing the for complication within first weeks after infection. However, nature processes underlying such aggravation remains unclear. Lipopolysaccharide derived from Gram-negative bacteria potent activator circulating immune cells including neutrophils, which foster through discharge neutrophil extracellular traps (NETs). Here, we use model endotoxinemia to link acute and subsequent activation...
Epidemiological studies have shown that women who use third-generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate a higher risk of venous thrombosis than second-generation OC levonorgestrel. It is also known mutation in factor V (factor V(Leiden)), which results resistance to activated protein C (APC) and the most common cause hereditary thrombophilia, potentiates prothrombotic effect OC. Effects APC on thrombin generation plasma using were compared response...
Factor V was purified from the plasma of an activated protein C (APC)-resistant patient who is homozygous for mutation Arg506→ Gln (factor VR506Q). VR506Q converted by thrombin into factor Va which further yielding a preparation that had same cofactor activity in prothrombin activation as normal Va. Inactivation low concentrations (<5 nM) 0.15 nM APC presence phospholipid vesicles proceeded via biphasic reaction consisted rapid phase (k = 4.3 × 107M−1s−1), intermediate with reduced fully...
Human coagulation factor V (FV) is an essential protein with functions in both the pro- and anticoagulant pathways. Failure to express control FV can either lead bleeding, or thromboembolic disease. Both events may develop into a life-threatening condition. Since first description of APC resistance, particular so-called V(Leiden) mutation, which prominent activated C cleavage site has been abolished through mutation gene, center attention thrombosis research. In this review we describe how...
Chemokines orchestrate leukocyte trafficking and function in health disease. Heterophilic interactions between chemokines a given microenvironment may amplify, inhibit, or modulate their activity; however, systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting surface plasmon resonance to obtain comprehensive map chemokine-chemokine confirm specificity. Structure-function analyses revealed that activity can be enhanced by CC-type heterodimers...
Significance Inflammation is a critical contributor to the pathogenesis of metabolic disorders associated with obesity. A group molecules crucial in regulating immune system are costimulatory molecules, including CD40. Our current study shows that CD40 acts as double-edged sword syndrome through initiation differential signaling cascades. The CD40-TNF receptor-associated factor (TRAF) 2/3/5 pathway protects against dysfunction and inflammation obesity; conversely, CD40-TRAF6 contributes...
Disrupting the HNP1 and CCL5 heteromer between neutrophils platelets blocks monocyte recruitment to inflammatory sites.
Coronavirus disease 19 (COVID-19) presents with severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels evolution damage associated molecular patterns (DAMPS) cell free DNA (cfDNA), extracellular histone H3 (H3) neutrophil elastase (NE), immune modulators GAS6 AXL in relation clinical parameters, ICU scoring systems mortality patients (n = 100) COVID-19. cfDNA, H3, NE, were increased COVID-19...
Mitochondrial complex I deficiency is the most common oxidative phosphorylation defect. Mutations have been detected in mitochondrial and nuclear genes, but genetics of many patients remain unresolved new genes are probably involved. In a consanguineous family, presented easy fatigability, exercise intolerance lactic acidosis blood from early childhood. muscle, subsarcolemmal proliferation severe were observed. Exercise activity was improved by supplement riboflavin at high dosage....
The pharmacophore concept is of central importance in computer-aided drug design (CADD) mainly because its successful application medicinal chemistry and, particular, high-throughput virtual screening (HTVS). simplicity the definition enables complexity molecular interactions between ligand and receptor to be reduced a handful set features. With many softwares available, it utmost interest explore behavior these tools when applied different biological systems. In this work, we present...
Generation of active procoagulant cofactor factor Va (FVa) and its subsequent association with the enzyme activated X (FXa) to form prothrombinase complex is a pivotal initial event in blood coagulation has been subject investigative effort, speculation, controversy. The current paradigm assumes that FV activation initiated by limited proteolysis traces (meizo) thrombin.Recombinant tick salivary protein TIX-5 was produced anticoagulant properties were studied use plasma, whole blood,...
Microcirculatory alterations play an important role in the early phase of sepsis. Shedding endothelial glycocalyx is regarded as a central pathophysiological mechanism causing microvascular dysfunction, contributing to multiple organ failure and death The objective this study was investigate whether thickness at stage septic patients relates clinical outcome. We measured perfused boundary region (PBR), which inversely proportional thickness, sublingual microvessels (5–25 µm) using sidestream...
Extracellular histones instigate an inflammatory triad - centered on cytotoxicity, immune cell stimulation, and coagulation ultimately shaping the dynamics outcome of various pathologies. Given virtual absence beneficial functions in extracellular space, recent years a number interference strategies have emerged. In this review we summarize pathogenic highlight current developments therapeutic interference. Finally, elaborate status preclinical attempts to interfere with context focus sepsis...