Search results for "Platelet"
showing 10 items of 786 documents
The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease
2018
Commensal gut microbiota have recently been implicated in cardiovascular disease (CVD) and cerebrovascular disease. Atherosclerotic plaque formation depends on the colonization status of the host. In addition to host nutrition and the related microbiota-dependent metabolic changes, activation of innate immune pathways triggers the development of atherosclerosis and supports arterial thrombosis. Gnotobiotic mouse models have uncovered that activation of Toll-like receptor-2 by gut microbial ligands supports von Willebrand factor-integrin mediated platelet deposition to the site of vascular injury. Depending on nutritional factors, the microbiota-derived choline-metabolite trimethylamine N-ox…
The Inflammatory Role of Platelets : Translational Insights from Experimental Studies of Autoimmune Disorders
2016
Beyond their indispensable role in hemostasis, platelets have shown to affect the development of inflammatory disorders, as they have been epidemiologically and mechanistically linked to diseases featuring an inflammatory reaction in inflammatory diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disorders. The identification of novel molecular mechanisms linking inflammation and to platelets has highlighted them as new targets for therapeutic interventions. In particular, genetic and pharmacological studies have identified an important role for platelets in neuroinflammation. This review summarizes the main molecular links between platelets and inflammation, focu…
The Serine/Threonine Protein Phosphatase 2A (PP2A) Regulates Syk Activity in Human Platelets
2020
Distinct membrane receptors activate platelets by Src-family-kinase (SFK)-, immunoreceptor-tyrosine-based-activation-motif (ITAM)-dependent stimulation of spleen tyrosine kinase (Syk). Recently, we reported that platelet activation via glycoprotein (GP) VI or GPIb&alpha
Comparative lipidomics and proteomics analysis of platelet lipid rafts using different detergents
2016
Lipid rafts play a pivotal role in physiological functions of platelets. Their isolation using nonionic mild detergents is considered as the gold standard method, but there is no consensual detergent for lipid raft studies. We aimed to investigate which detergent is the most suitable for lipid raft isolation from platelet membrane, based on lipidomics and proteomics analysis. Platelets were obtained from healthy donors. Twelve sucrose fractions were extracted by three different detergents, namely Brij 35, Lubrol WX, and Triton X100, at 0.05% and 1%. After lipidomics analysis and determination of fractions enriched in cholesterol (Ch) and sphingomyelin (SM), proteomics analysis was performed…
The Neutrophil Secretome as a Crucial Link between Inflammation and Thrombosis
2021
Cardiovascular diseases are a leading cause of death. Blood–cell interactions and endothelial dysfunction are fundamental in thrombus formation, and so further knowledge of the pathways involved in such cellular crosstalk could lead to new therapeutical approaches. Neutrophils are secretory cells that release well-known soluble inflammatory signaling mediators and other complex cellular structures whose role is not fully understood. Studies have reported that neutrophil extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) contribute to thrombosis. The objective of this review is to study the role of EVs and NETs as key factors in the transition from inflammation to thrombo…
Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in platelet plasma membrane
2017
Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels. Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2, CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treate…
Native, Intact Glucagon-Like Peptide 1 Is a Natural Suppressor of Thrombus Growth Under Physiological Flow Conditions
2020
Objective: In patients with diabetes mellitus, increased platelet reactivity predicts cardiac events. Limited evidence suggests that DPP-4 (dipeptidyl peptidase 4) influences platelets via GLP-1 (glucagon-like peptide 1)-dependent effects. Because DPP-4 inhibitors are frequently used in diabetes mellitus to improve the GLP-1-regulated glucose metabolism, we characterized the role of DPP-4 inhibition and of native intact versus DPP-4-cleaved GLP-1 on flow-dependent thrombus formation in mouse and human blood. Approach and Results: An ex vivo whole blood microfluidics model was applied to approach in vivo thrombosis and study collagen-dependent platelet adhesion, activation, and thrombus for…
The Gut Microbiota as an Influencing Factor of Arterial Thrombosis
2018
The mutualistic gut microbiota does not only impact the development and function of various immune cell types, but it also influences the function of the hepatic vascular endothelium and prothrombotic platelet function. With germ-free mouse models, we have demonstrated that gut-derived microbial-associated molecular patterns could stimulate hepatic von Willebrand factor (VWF) synthesis and plasmatic VWF levels through Toll-like receptor-2 (TLR2), thus defining the extent of platelet deposition to the subendothelial matrix of the ligation-injured common carotid artery. In addition to the microbiota-derived choline metabolite trimethylamine N-oxide and the microbiota's regulatory role on the …
Platelet, Not Endothelial, P-Selectin Expression Contributes to Generation of Immunity in Cutaneous Contact Hypersensitivity
2010
Leukocyte extravasation is a prerequisite for host defense and autoimmunity alike. Detailed understanding of the tightly controlled and overlapping sequences of leukocyte extravasation might aid development of novel therapeutic strategies. Leukocyte extravasation is initiated by interaction of selectins with appropriate carbohydrate ligands. Lack of P-selectin expression leads to decreased contact hypersensitivity responses. Yet, it remains unclear if this is due to inhibition of leukocyte extravasation to the skin or due to interference with initial immune activation in lymph nodes. In line with previous data, we here report a decreased contact hypersensitivity response, induced by 2,4,-di…
Demonstration of High-Affinity Binding Sites for C3a Anaphylatoxin on Guinea-Pig Platelets
1978
3H-serotonin release from guinea-pig platelets was demonstrated to be the consequence of C3a binding to these cells. A Scatchard analysis of dose-response data of the 125I-C3a binding pattern to guinea-pig platelets pointed to the existence of binding sites with high and low affinity for the C3a molecule (HA and LA receptors). HA receptors are specific for C3a with intact C-terminal arginine. whereas C3adesarg only interacts with LA receptors. The release of serotonin may be induced by a combined reaction of C3a with HA receptors and LA receptors on the platelet membrane.