A5015042844- Blood Coagulation and Thrombosis Mechanisms
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Vitamin K Research Studies
- Chemical Synthesis and Analysis
- Platelet Disorders and Treatments
- Cell Adhesion Molecules Research
- Venous Thromboembolism Diagnosis and Management
- Peptidase Inhibition and Analysis
- Atrial Fibrillation Management and Outcomes
- Protease and Inhibitor Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Atherosclerosis and Cardiovascular Diseases
- Venomous Animal Envenomation and Studies
- Chemokine receptors and signaling
- Galectins and Cancer Biology
- Blood properties and coagulation
- Radiopharmaceutical Chemistry and Applications
- Complement system in diseases
- Biochemical and Structural Characterization
- Heparin-Induced Thrombocytopenia and Thrombosis
- Antiplatelet Therapy and Cardiovascular Diseases
- S100 Proteins and Annexins
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Maastricht University
2016-2025
Maastricht University Medical Centre
2009-2023
Sheba Medical Center
2023
Université de Bordeaux
2023
Biologie des maladies cardiovasculaires
2023
Washington University in St. Louis
2013-2023
Inserm
2005-2023
National Hemophilia Foundation
2023
Canisius-Wilhelmina Ziekenhuis
2020
Cardiovascular Institute Hospital
2004-2018
The total chemical synthesis of proteins has great potential for increasing our understanding the molecular basis protein function. introduction native ligation techniques to join unprotected peptides next a cysteine residue greatly facilitated moderate size. Here, we describe straightforward methodology that enabled us rapidly analyze compatibility strategy X–Cys sites, where X is any 20 naturally occurring amino acids. simplified avoids necessity specific acid thioester linkers or...
Aniline acts as a nucleophilic catalyst of oxime ligation in aqueous solution through formation the orange-colored intermediate. The method is demonstrated by acceleration peptides at pH 4.5 and 7, which extends scope this reaction to conditions relevant for bioconjugation macromolecules (see scheme). Imine-based reactions have found wide application conjugation biomolecules result their high chemoselectivity.1–8 Aldehydes ketones can be readily introduced into are virtually inert towards...
Aniline accelerates hydrazone formation and transimination through nucleophilic catalysis. To demonstrate the method, unprotected peptides are reacted then scrambled using a reaction under conditions relevant for biological applications. The strong enhancement in rate of equilibration broadens scope this stable imine field dynamic covalent chemistry.
Rationale: Acute lung injury (ALI) causes high mortality, but its molecular mechanisms and therapeutic options remain ill-defined. Gram-negative bacterial infections are the main cause of ALI, leading to neutrophil infiltration, permeability increases, deterioration gas exchange, damage. Platelets activated during insights into their mechanistic contribution accumulation in elusive.Objectives: To determine platelet-mediated recruitment ALI.Methods: Interference with platelet–neutrophil...
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...
Tissue factor (TF) plays an important role in hemostasis, inflammation, angiogenesis, and the pathophysiology of atherosclerosis cancer. In this article we uncover a mechanism which protein S, is well known as cofactor activated C, specifically inhibits TF activity by promoting interaction between full-length pathway inhibitor (TFPI) Xa (FXa). The stimulatory effect S on FXa inhibition TFPI caused 10-fold reduction K(i) FXa/TFPI complex, decreased from 4.4 nM absence to 0.5 presence S. This...
Tumor angiogenesis is a key event in cancer progression. Here, we report that tumors can stimulate tumor by secretion of galectin-1. growth and different models are hampered galectin-1-null (gal-1(-/-)) mice. However, less affected when cells express secrete high levels Furthermore, endothelial gal-1(-/-) mice take up galectin-1 secreted cells. Uptake cultured specifically promotes H-Ras signaling to the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (Erk)...
Thrombin generation in vivo may be important regulating atherosclerotic progression. In the present study, we examined for first time activity and presence of relevant coagulation proteins relation to progression atherosclerosis.Both early stable advanced lesions were collected pairwise from each individual (n=27) during autopsy. Tissue homogenates prepared both total plaques isolated plaque layers, which factors (F) II, X, XII tissue factor was determined. Microarray analysis implemented...
<i>Objective:</i> Matrix γ-carboxyglutamate (Gla) protein (MGP) is a vitamin K-dependent and strong inhibitor of vascular calcification. Vitamin K deficiency leads to inactive uncarboxylated MGP (ucMGP), which accumulates at sites arterial We hypothesized that as result ucMGP deposition around calcification, the circulating fraction decreased. Here we report on development an assay potential diagnostic utility monitoring serum levels. <i>Methods Results:</i> An...
A quantum-dot-based nanoparticle is presented, allowing visualization of cell death and activated platelets with fluorescence imaging MRI. The particle exhibits intense a large MR relaxivity (r1) 3000−4500 mM-1 s-1 per due to newly designed construct increasing the gadolinium-DTPA load. suitable for both anatomic subcellular structures in vessel wall promising bimodal contrast agent future vivo studies.
The multivalent character of dendrimers has positioned these well-defined, highly branched macromolecules at the forefront in development new contrast agents for biomedical magnetic resonance imaging (MRI). By modifying periphery dendrimer with gadolinium(III) chelates, relaxivity resulting MRI agent is increased considerably, compared to low molecular weight Gd(III) chelates. monodisperse creates a unique opportunity introduce dendritic into clinics. In addition, prolonged vascular...
Background: The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of has only been implied through pharmacological intervention, in particular, because the somatic deletion CXCR4 gene mice is embryonically lethal. Moreover, cell-specific effects arterial wall underlying mechanisms remain elusive, prompting us to investigate relevance vascular types for atheroprotection. Methods: We examined atherosclerosis...
The leukocyte response in acute inflammation is characterized by an initial recruitment of neutrophils preceding a second wave monocytes. Neutrophil-derived granule proteins were suggested to hold important role this cellular switch. exact mechanisms which mediate these processes are only partially understood.To investigate the and their contents adhesion monocyte subpopulations inflammation.Here, we show that neutrophil-derived cathelicidins (human: LL37, mouse: CRAMP) induce classical...
The molecular pathways that control the wound healing after myocardial infarction (MI) are not completely elucidated. One of these is Wnt/Frizzled pathway. In this study, we evaluated Frizzled as a novel therapeutic target for MI. These proteins act receptors Wnt and were previously shown to be expressed in infarct.Wnt/Frizzled signaling has been studied decades, but synthetic ligands interfere with interaction between Wnts have described date. Here report selection 3 peptides derived from...
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...
Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2-infected patients. Vitamin K activates both hepatic coagulation factors extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin insufficiency, procoagulant preferentially activated over proteins. also matrix Gla (MGP), which protects against pulmonary vascular elastic fiber damage. We hypothesized that may be implicated disease 2019...