A5013189164- Platelet Disorders and Treatments
- Protease and Inhibitor Mechanisms
- Blood properties and coagulation
- Blood Coagulation and Thrombosis Mechanisms
- Antiplatelet Therapy and Cardiovascular Diseases
- Acute Ischemic Stroke Management
- Lipoproteins and Cardiovascular Health
- Venous Thromboembolism Diagnosis and Management
- Cell Adhesion Molecules Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Blood groups and transfusion
- Heparin-Induced Thrombocytopenia and Thrombosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Intracerebral and Subarachnoid Hemorrhage Research
- Cerebrovascular and Carotid Artery Diseases
- Monoclonal and Polyclonal Antibodies Research
- Adipokines, Inflammation, and Metabolic Diseases
- Eosinophilic Disorders and Syndromes
- Chronic Myeloid Leukemia Treatments
- Cerebral Venous Sinus Thrombosis
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neurological Disorders and Treatments
- Systemic Sclerosis and Related Diseases
Laboratoire de Recherche Vasculaire Translationnelle
2014-2025
Inserm
2016-2025
Université Paris Cité
2015-2025
Université Sorbonne Paris Nord
2012-2024
Sorbonne Paris Cité
2013-2024
Sorbonne Université
2011-2024
Hôpital Bichat-Claude-Bernard
2006-2022
Assistance Publique – Hôpitaux de Paris
2011-2020
Délégation Paris 7
2011-2019
Université de Toulouse
2019
Background and Purpose— Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones granular proteins produced by activated neutrophils. NETs have been identified as major triggers structural factors of thrombosis. A recent study designated threads from a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim this was to assess the presence thrombi retrieved during...
Downstream microvascular thrombosis (DMT) is known to be a contributing factor incomplete reperfusion in acute ischemic stroke. The aim of this study was determine the timing DMT with intravital imaging and test hypothesis that intravenous alteplase infusion could reduce transient middle cerebral artery occlusion (MCAO) rat stroke model.Rats were subjected 60-minute MCAO. Alteplase (10 mg/kg) administered 30 minutes after beginning Real-time fluorescence microscopy through dura-sparing...
Background and Purpose— Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How impacts the pathophysiology of stroke remains largely unknown. We investigated how preexisting increases ischemia/reperfusion cerebral injury. Methods— Normoglycemic streptozotocin-treated hyperglycemic rats were subjected to transient middle artery occlusion. Infarct growth brain perfusion assessed by magnetic resonance imaging. Markers platelet, coagulation, neutrophil activation...
Objectives Behçet’s disease (BD) is a chronic systemic vasculitis. Thrombosis frequent and life-threatening complication. The pathogenesis of BD poorly understood evidence supporting role for primed neutrophils in BD-associated thrombotic risk scant. To respond to inflammatory insults, release web-like structures, known as neutrophil extracellular traps (NETs), which are prothrombotic. We evaluated the NETs markers BD. Methods Blood samples were collected from patients with BD, according...
Thrombi responsible for large vessel occlusion (LVO) in the setting of acute ischemic stroke (AIS) are characterized by a low recanalization rate after IV thrombolysis. To test whether AIS thrombi have inherent common features that limit their susceptibility to thrombolysis, we analyzed composition and ultrastructural organization causing LVO.A total 199 endovascular thrombectomy-retrieved were immunohistology scanning electron microscopy (SEM) subjected ex vivo thrombolysis assay. The...
Glycoprotein VI, a major platelet activation receptor for collagen and fibrin, is considered particularly promising, safe antithrombotic target. In this study, we show that human glycoprotein VI signals upon adhesion to fibrinogen. Full spreading of platelets on fibrinogen was abolished in from VI- deficient patients suggesting activates through VI. While mouse failed spread fibrinogen, human-glycoprotein VI-transgenic showed full increased Ca2+ signaling the tyrosine kinase Syk. Direct...
Objective— The immune receptor homologue glycoprotein VI (GPVI)/FcR γ chain complex is primarily responsible for platelet activation by collagen. There growing evidence that optimal binding of GPVI to collagen depends on the assembly dimers. valence resting platelets needs be clearly established because avidity would greater if constitutively expressed as a dimer than monomer. Methods and Results— Using monoclonal antibody (9E18) preferentially binds dimers, we found was maintained in...
Various studies using proteomic approaches have shown that HDL can carry many proteins other than its constitutive apolipoprotein A-I (apoA-I). Using mass spectrometry and Western blotting, we showed the presence of alpha(1)-antitrypsin (AAT) (SERPINA1, serpin peptidase inhibitor, clade A, an elastase inhibitor) in HDL, isolated either by ultracentrifugation or selected-affinity immunosorption anti-apoA-I column. Furthermore, report possesses potent antielastase activity. We further only but...
Objective: Atherothrombosis occurs upon rupture of an atherosclerotic plaque and leads to the formation a mural thrombus. Computational fluid dynamics numerical models indicated that mechanical stress applied thrombus increases dramatically as grows, strong inter-platelet interactions are essential maintain its stability. We investigated whether GPVI (glycoprotein VI)-mediated platelet activation helps stability by using real-time video-microscopy. Approach Results: showed blockade with 2...
Background Fibrosis, which is characterized by the pathological accumulation of collagen, recognized as an important feature many chronic diseases, and such, constitutes enormous health burden. We need non-invasive specific methods for early diagnosis follow-up fibrosis in various disorders. Collagen targeting molecules are therefore interest potential vivo imaging fibrosis. In this study, we developed a collagen-specific probe using new approach that takes advantage inherent specificity...
Protease nexin-1 (PN-1) is a serpin that inhibits plasminogen activators, plasmin, and thrombin. PN-1 barely detectable in plasma, but we have shown recently present within the α-granules of platelets.In this study, role platelet fibrinolysis was investigated with use human platelets incubated blocking antibody from PN-1-deficient mice. We showed by using fibrin-agar zymography fibrin matrix inhibited both generation plasmin fibrin-bound tissue activator activity itself. Rotational...
Abstract Platelet glycoprotein VI (GPVI) is attracting interest as a potential target for the development of new antiplatelet molecules with low bleeding risk. GPVI binding to vascular collagen initiates thrombus formation and interactions fibrin promote growth stability thrombus. In this study, we show that glenzocimab, clinical stage humanized antibody fragment (Fab) high affinity GPVI, blocks both ligands through combination steric hindrance structural change. A cocrystal glenzocimab an...
Glycoprotein VI (GPVI) has been proposed as a promising antiplatelet target, because its blockade prevents experimental thrombosis without impairing hemostasis. The objective of this study was to develop preclinical tool evaluate the role human GPVI (hGPVI) in various models and screen anti-GPVI compounds. A genetically modified mouse strain expressing hGPVI developed using knockin strategy. mice were viable fertile did not present any hematological defects. Approximately 3700 copies...
Platelets are not only central actors of hemostasis and thrombosis but also other processes including inflammation, angiogenesis, tissue regeneration. Accumulating evidence indicates that these "non classical" functions platelets do necessarily rely on their well-known ability to form thrombi upon activation. This suggests the existence non-thrombotic alternative states We investigated this possibility through dose-response analysis thrombin- collagen-induced changes in platelet phenotype,...
We have previously reported that intravenous injection of high-density lipoproteins (HDLs) was neuroprotective in an embolic stroke model. hypothesized HDL vasculoprotective actions on the blood-brain barrier (BBB) may decrease hemorrhagic transformation-associated with tissue plasminogen activator (tPA) administration acute stroke.We used tPA alone or combination HDLs vivo 2 models focal middle cerebral artery occlusion (MCAO) (embolic and 4-hour monofilament MCAO) vitro a model BBB....
Cerebral venous sinus thrombosis (CVST) is an uncommon thromboembolic event accounting for <1% of strokes resulting in brain parenchymal injuries. JAK2V617F mutation, the most frequent driving mutation myeloproliferative neoplasms, has been reported to be associated with worse clinical outcomes patients CVST. We investigated whether hematopoietic expression predisposes specific pathophysiological processes and/or prognosis after Using vivo mouse model CVST, we analyzed clinical, biological,...
Exposure of platelets to collagen triggers the formation a platelet clot. Pharmacological agents capable inhibiting activation by are thus potential therapeutic interest. Thrombus is initiated interaction GPIb-V-IX complex with collagen-bound vWF, while GPVI that reinforced ADP and thromboxane A2. Losartan an angiotensin II (Ang II) type I receptor (AT1R) antagonist proposed have antiplatelet activity via inhibition both A2 (TXA2) (TP) glycoprotein VI (GPVI). Here, we characterized in vitro...
Objective— Despite the high clinical relevance of thrombolysis, models for its study in human flowing blood are lacking. Our objective was to develop a microfluidic model comparative evaluation thrombolytic therapeutic strategies. Approach and Results— Citrated supplemented with 3,3′-dihexyloxacarbocyanine iodide Alexa Fluor 647 fibrinogen conjugate, recalcified, perfused 3 4 minutes at venous or arterial wall shear rate flow chambers coated collagen tissue factor generate nonocclusive...