A5091194864- Platelet Disorders and Treatments
- Cell Adhesion Molecules Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Blood properties and coagulation
- Blood Coagulation and Thrombosis Mechanisms
- Ion Channels and Receptors
- Acute Ischemic Stroke Management
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Mast cells and histamine
- Proteoglycans and glycosaminoglycans research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Venous Thromboembolism Diagnosis and Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Hematopoietic Stem Cell Transplantation
- Systemic Lupus Erythematosus Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory Biomarkers in Disease Prognosis
- Diabetes and associated disorders
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Phytochemicals and Antioxidant Activities
- Diabetes Management and Research
- Barrier Structure and Function Studies
- Cholesterol and Lipid Metabolism
Universitätsklinikum Würzburg
2016-2025
University of Würzburg
2016-2025
Bayer (Germany)
2023
Institute for Biomedicine
2013-2023
Établissement Français du Sang
2020
Centre Virchow-Villermé
2011-2017
University Medical Center Hamburg-Eppendorf
2016
Universität Hamburg
2016
University of Duisburg-Essen
2016
University of Regensburg
2016
Excessive cytosolic calcium ion (Ca(2+)) accumulation during cerebral ischemia triggers neuronal cell death, but the underlying mechanisms are poorly understood. Capacitive Ca(2+) entry (CCE) is a process whereby depletion of intracellular stores causes activation plasma membrane channels. In nonexcitable cells, CCE controlled by endoplasmic reticulum (ER)-resident sensor STIM1, whereas closely related protein STIM2 has been proposed to regulate basal and ER concentrations make only minor...
In the absence of PLD1, platelets do not form stable aggregates under high shear conditions.
Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins participate in thrombus formation and hemostasis. Proteins stored α-granules also thought to play a role inflammation wound healing, but their functional significance vivo is unknown. Mutations NBEAL2 have been linked gray syndrome (GPS), rare bleeding disorder characterized by macrothrombocytopenia,...
Abstract In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets, required for hemostasis and thrombosis. MKs originate from hematopoietic stem cells are thought to migrate an endosteal niche towards vascular sinusoids during their maturation. Through imaging of intact BM, here we show that can be found within entire without a bias bone-distant regions. By combining vivo two-photon microscopy situ light-sheet fluorescence with computational simulations, reveal...
Ischemic stroke is a leading cause of morbidity and mortality worldwide. Recanalization the occluded vessel essential but not sufficient to guarantee brain salvage. Experimental clinical data suggest that infarcts often develop further due thromboinflammatory process critically involving platelets T cells, underlying mechanisms are unknown.
Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil platelet lineages extends to the earliest stages of formation by megakaryocytes bone marrow. Using intravital microscopy, we show "plucked" intravascular megakaryocyte extensions, termed proplatelets, control production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal...
Abstract Background and Aims Glycoprotein VI (GPVI) is a platelet collagen/fibrin(ogen) receptor an emerging pharmacological target for the treatment of thrombotic thrombo-inflammatory diseases, notably ischaemic stroke. A first anti-human GPVI (hGPVI) antibody Fab-fragment (ACT017/glenzocimab, KD: 4.1 nM) recently passed clinical phase 1b/2a study in patients with acute stroke was found to be well tolerated, safe, potentially beneficial. In this study, novel humanized anti-GPVI (EMA601;...
In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca(2+) entry (SOCE) with Orai1 principal channel. Both proteins contribute to collagen-dependent arterial thrombosis mice vivo. It is unclear whether STIM2 involved. A platelet response relying on surface exposure of phosphatidylserine (PS), which accomplishes procoagulant activity. We studied this mouse platelets deficient STIM1, STIM2, or Orai1. Upon high shear flow blood over collagen, Stim1(-/-) and...
Abstract Calcium (Ca2+) signaling in T lymphocytes is essential for a variety of functions, including the regulation differentiation, gene transcription, and effector functions. A major Ca2+ entry pathway nonexcitable cells, store-operated (SOCE), wherein depletion intracellular stores upon receptor stimulation causes subsequent influx extracellular across plasma membrane. Stromal interaction molecule (STIM) 1 sensor endoplasmic reticulum, which controls this process, whereas other STIM...
Activation of microglia is the first and main immune response to brain injury. Release nucleotides ATP, ADP, UDP from damaged cells regulate microglial migration phagocytosis via purinergic P2Y receptors. We hypothesized that store-operated Ca(2+) entry (SOCE), prevalent influx mechanism in non-excitable cells, a potent mediator responses extracellular nucleotides. Expression analyses STIM sensors Orai channel subunits, comprise molecular machinery SOCE, showed relevant levels STIM1, STIM2,...
Ischemic stroke, which is mainly caused by thromboembolic occlusion of brain arteries, the second leading cause death and disability worldwide with limited treatment options. The platelet collagen receptor glycoprotein VI (GPVI) a key player in arterial thrombosis critical determinant stroke outcome, making its signaling pathway an attractive target for pharmacological intervention. spleen tyrosine kinase (Syk) essential mediator downstream not only GPVI but also other immune cell receptors....
We recently showed that mice lacking the lipid signaling enzyme phospholipase (PL) D1 or both PLD isoforms (PLD1 and PLD2) were protected from pathological thrombus formation ischemic stroke, whereas hemostasis was not impaired in these animals. sought to assess whether pharmacological inhibition of activity affects hemostasis, thrombosis, thrombo-inflammatory brain infarction mice.Treatment platelets with reversible, small molecule inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI),...
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show the small GTPases Cdc42 RhoA act as a regulatory circuit downstream of MK-specific mechanoreceptor GPIb coordinate polarized platelet biogenesis. Functional deficiency either or...
Rationale: In patients after acute myocardial infarction (AMI), the initial extent of necrosis and inflammation determine clinical outcome. One early event in AMI is increased cardiac expression atrial natriuretic peptide (NP) B-type NP, with their plasma levels correlating severity ischemia. It was shown that NPs, via cGMP-forming guanylyl cyclase-A (GC-A) receptor cGMP-dependent kinase I (cGKI), strengthen systemic endothelial barrier properties inflammation. Objective: We studied whether...