A5068782139- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Venous Thromboembolism Diagnosis and Management
- Antiplatelet Therapy and Cardiovascular Diseases
- COVID-19 Clinical Research Studies
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cell Adhesion Molecules Research
- Blood properties and coagulation
- Heparin-Induced Thrombocytopenia and Thrombosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Atrial Fibrillation Management and Outcomes
- Long-Term Effects of COVID-19
- Acute Ischemic Stroke Management
- Blood groups and transfusion
- Peripheral Artery Disease Management
- Cerebrovascular and Carotid Artery Diseases
- COVID-19 and healthcare impacts
- Ion Channels and Receptors
- Rheumatoid Arthritis Research and Therapies
- Diabetes Treatment and Management
- Atherosclerosis and Cardiovascular Diseases
- Diet, Metabolism, and Disease
- Vasculitis and related conditions
- Climate Change and Health Impacts
- Ion channel regulation and function
Maastricht University
2017-2025
Maastricht University Medical Centre
2021-2024
Utrecht University
2023
University Medical Center Utrecht
2023
Cardiovascular Institute Hospital
2018-2022
Abstract The leading cause of heart disease in developed countries is coronary atherosclerosis, which not simply a result ageing but chronic inflammatory process that can lead to acute clinical events upon atherosclerotic plaque rupture or erosion and arterial thrombus formation. composition location plaques determine the phenotype lesion whether it more likely erode. Although both initiate platelet activation on exposed vascular surface, contribution platelets formation differs between two...
In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based assessment of the inter- and intra-subject variability parameters microspot-based formation, we aimed to determine factors contributing this variation. Blood samples from 94 genotyped healthy subjects were analyzed for conventional phenotyping: i.e. hematologic parameters, glycoprotein (GP) expression levels activation markers (24...
Atherosclerotic plaque development depends on chronic inflammation of the arterial wall. A dysbiotic gut microbiota can cause low-grade inflammation, and composition was linked to cardiovascular disease risk. However, role this environmental factor in atherothrombosis remains undefined. To analyze impact atherothrombosis, we rederived low-density lipoprotein receptor-deficient (Ldlr-/- ) mice as germfree (GF) kept these for 16 weeks an atherogenic high-fat Western diet (HFD) under GF...
Abstract Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step realize GWAS potential in introduction precision medicine. Here we set out determine mechanisms underpinning variant association platelet quantitative using cell type-matched epigenomic data and promoter long-range interactions. We identify regulatory functions for 423 565 (75%) demonstrate, through ex vivo proof principle genome editing validation,...
Abstract Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets coagulation proteases, interacting with circulating cells in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed audience members results these discussions incorporated final document that...
The role of glycoprotein VI (GPVI) in platelets was investigated 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to transmembrane domain, leading expression truncated protein cytoplasm devoid region. Western blotting and flow cytometry GP6hom (homozygous) confirmed loss full protein. level Fc receptor γ-chain, which associates with GPVI membrane, partially reduced, but other receptors signaling proteins not altered. Spreading on collagen von...
The activation of platelets and coagulation at vascular injury sites is crucial for haemostasis but can promote thrombosis inflammation in pathologies. Here, we delineate an unexpected spatio-temporal control mechanism thrombin activity that platelet orchestrated locally limits excessive fibrin formation after initial haemostatic deposition. During activation, the abundant glycoprotein (GP) V cleaved by thrombin. We demonstrate with genetic pharmacological approaches thrombin-mediated...
Acute ischemic stroke (AIS) is the most common type of and requires immediate reperfusion. Current acute reperfusion therapies comprise administration intravenous thrombolysis and/or endovascular thrombectomy. Although these are increasingly successful, optimized secondary antithrombotic treatment remains warranted, specifically to reduce risk major bleeding complications. In development AIS, coagulation platelet activation play crucial roles by driving occlusive clot formation. Recent...
Despite the increasing demand for small-caliber tissue-engineered vascular grafts (sTEVGs), currently there are no clinically available substitutes due to graft failure, mainly because of thrombotic events. We purified a fucosylated chondroitin sulphate from two marine invertebrates, echinoderm Holothuria tubulosa (Ht) and sponge Sarcotragus spinosulus (Ss), exhibiting interesting anticoagulant activities in vitro cytocompatibility. This study aimed exploit properties these polysaccharides...
Background Endovascular catheters and devices used for thrombectomy in patients who had a stroke can damage the vessel lumen leading to microthrombi. During recanalisation, microthrombi could migrate distally occlude cerebral microvasculature, potentially limiting benefit of recanalisation therapy. Objectives To describe vascular injury occurring after endovascular therapy (EVT), with stent retrievers (SR) direct aspiration (DA), open up avenues further improvement EVT technique. Methods SR...
In patients with dysfunctions of the Ca2+ channel ORAI1, stromal interaction molecule 1 (STIM1) or integrin-regulating kindlin-3 (FERMT3), severe immunodeficiency is frequently linked to abnormal platelet activity. this paper, we studied responsiveness by multiparameter assessment whole blood thrombus formation under high-shear flow conditions in 9 patients, including relatives, confirmed rare genetic mutations STIM1 FERMT3. platelets isolated from 5 out 6 ORAI1 mutations, store-operated...
Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was investigate serum biomarkers coagulation activation, microvascular dysfunction, and persisting two years after acute COVID-19.Patients diagnosed SARS-CoV-2 infection between February June 2020 were recruited. Outcome measures included...
IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is associated with a clear prothrombotic phenotype. Although the exact pathophysiological mechanisms are not yet fully understood, thrombosis clearly highly important in prognosis and outcome of COVID-19. As such, there need for diagnostic analysis quantification coagulation potential these patients, both at diagnosis follow-up. Global assays like thrombin generation (TG) rotational thromboelastometry (ROTEM)...
Abstract The risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV); however, detailed understanding the underlying mechanisms hypercoagulability limited. We assessed prospectively different coagulation parameters 71 active AAV at baseline and after 6 months follow-up. D-dimers fibrinogen were most presentation remained elevated half patients. Particularly, thrombin-antithrombin (T:AT) complex activated...
Losartan and honokiol are small molecules which have been described to inhibit aggregation of platelets by collagen. has proposed block clustering GPVI but not affect binding Honokiol reported bind directly only at a concentration that is three orders magnitude higher than needed for inhibition aggregation. The mechanism action both inhibitors so far unclear. In the present study, we confirm inhibitory effects agents on platelet collagen show also induced activation CLEC-2 or low affinity...