keyword
MENU ▼
Read by QxMD icon Read
search

GPVI

keyword
https://www.readbyqxmd.com/read/29567387/the-spatial-molecular-pattern-of-integrin-recognition-sites-and-their-immobilization-to-colloidal-nanobeads-determine-%C3%AE-2%C3%AE-1-integrin-dependent-platelet-activation
#1
Augusto Martins Lima, Seraphine V Wegner, Ana C Martins Cavaco, Maria Inacia Estevão-Costa, Raquel Sanz-Soler, Stephan Niland, Georgii Nosov, Jürgen Klingauf, Joachim P Spatz, Johannes A Eble
Collagen, a strong platelet activator, is recognized by integrin α2β1 and GPVI. It induces aggregation, if added to suspended platelets, or platelet adhesion if immobilized to a surface. The recombinant non-prolylhydroxylated mini-collagen FC3 triple helix containing one α2β1 integrin binding site is a tool to specifically study how α2β1 integrin activates platelet. Whereas soluble FC3 monomers antagonistically block collagen-induced platelet activation, immobilization of several FC3 molecules to an interface or to colloidal nanobeads determines the agonistic action of FC3...
March 16, 2018: Biomaterials
https://www.readbyqxmd.com/read/29559479/oral-bruton-tyrosine-kinase-inhibitors-selectively-block-atherosclerotic-plaque-triggered-thrombus-formation
#2
Kristina Busygina, Janina Jamasbi, Till Seiler, Hans Deckmyn, Christian Weber, Richard Brandl, Reinhard Lorenz, Wolfgang Siess
Interaction of Von Willebrand factor (VWF) with platelet glycoprotein (GP) Ib and of collagen with GPVI is essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk) which can irreversibly be blocked by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long term safety. We found that ibrutinib and the novel Btk-inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid...
March 20, 2018: Blood
https://www.readbyqxmd.com/read/29512284/the-chaperone-protein-hsp47-a-platelet-collagen-binding-protein-that-contributes-to-thrombosis-and-haemostasis
#3
P Sasikumar, K S AlOuda, W J Kaiser, L M Holbrook, N Kriek, J A Unsworth, A P Bye, T Sage, R Ushioda, K Nagata, R W Farndale, J M Gibbins
OBJECTIVE: Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering haemostasis and thrombosis, in this study we sought to characterise the role of HSP47 on these cells. APPROACH AND RESULTS: The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered...
March 7, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29472360/immobilized-fibrinogen-activates-human-platelets-through-gpvi
#4
Pierre H Mangin, Marie-Blanche Onselaer, Nicolas Receveur, Nicolas Le Lay, Alexander T Hardy, Clare Wilson, Ximena Sanchez, Stephane Loyau, Arnaud Dupuis, Amir K Babar, Jeanette Lc Miller, Helen Philippou, Craig E Hughes, Andrew B Herr, Robert As Ariëns, Diego Mezzano, Martine Jandrot-Perrus, Christian Gachet, Steve P Watson
GPVI, a major platelet activation receptor for collagen and fibrin, is considered as a particularly promising safe antithrombotic target. In this study, we show that human GPVI signals upon platelet adhesion to fibrinogen. Full spreading of human platelets on fibrinogen is abolished in platelets from GPVI-deficient patients suggesting that fibrinogen activates platelets through GPVI. While mouse platelets fail to spread on fibrinogen, human-GPVI-transgenic mouse platelets show full spreading and increased Ca2+ signalling through the tyrosine kinase Syk...
February 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29446689/platelets-and-vascular-integrity
#5
Carsten Deppermann
Platelets patrol the vasculature and adhere at sites of vascular damage after trauma to limit blood loss. In recent years, however, it has become clear that platelets also contribute to pathophysiologic processes such as thrombosis, atherosclerosis, stroke, sepsis and many more. An exciting new role for them is in non-classical hemostasis to prevent bleeding in the inflamed vasculature. Recent studies suggest that GPVI, CLEC-2, integrin αIIbβ3 (GPIIb/IIIa), and the content of platelet α- and dense granules are important players in this process...
February 15, 2018: Platelets
https://www.readbyqxmd.com/read/29437639/soluble-gpvi-is-elevated-in-injured-patients-shedding-is-mediated-by-fibrin-activation-of-gpvi
#6
Samantha J Montague, Céline Delierneux, Christelle Lecut, Nathalie Layios, Robert J Dinsdale, Christine S-M Lee, Natalie S Poulter, Robert K Andrews, Peter Hampson, Christopher M Wearn, Nathalie Maes, Jonathan Bishop, Amy Bamford, Chris Gardiner, Woei Ming Lee, Tariq Iqbal, Naiem Moiemen, Steve P Watson, Cécile Oury, Paul Harrison, Elizabeth E Gardiner
Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU) for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29407628/intraplatelet-reactive-oxygen-species-ros-correlate-with-the-shedding-of-adhesive-receptors-microvesiculation-and-platelet-adhesion-to-collagen-during-storage-does-endogenous-ros-generation-downregulate-platelet-adhesive-function
#7
Mehran Ghasemzadeh, Ehteramolsadat Hosseini, Zahra Oushyani Roudsari, Parvin Zadkhak
Platelets storage lesion is mainly orchestrated by platelet activating signals during storage. Reactive oxygen species (ROS) are being considered as important signaling molecules modulating platelet function while their production has also been shown to be augmented by platelet activation. This study investigated to what extent endogenous ROS generation during platelet storage could be correlated with platelet receptor shedding, microvesiculation and adhesive function. 10 PRP-platelet concentrates were subjected to flow cytometry analysis to examine the generation of intraplatelet ROS on days 1, 5 and 7 after storage...
February 1, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29395079/ceramidase-critically-affects-gpvi-dependent-platelet-activation-and-thrombus-formation
#8
Patrick Münzer, Sophie Mittelstädt, Sascha Geue, Mailin-Christin Manke, Britta Walker-Allgaier, Florian Lang, Meinrad Gawaz, Oliver Borst
Platelet aggregation, dense granule secretion and thrombus formation are dependent on sphingolipids like ceramide and sphingosine as well as sphingosine-1 phosphate. Sphingosine/ceramide metabolism involves ceramide synthases and ceramidases. However, the role of ceramide synthase and ceramidase in the regulation of platelet function remained ill-defined. The present study determined transmission light aggregometry, employed luciferase based ATP release measurements and studied in vitro thrombus formation under high arterial shear rates in order to define the impact of pharmacological inhibition of serine palmitoyltransferase, ceramide synthase and ceramidase on platelet function...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29378359/dimeric-glycoprotein-vi-binds-to-collagen-but-not-to-fibrin
#9
Mariam Ebrahim, Janina Jamasbi, Kristin Adler, Remco T A Megens, Yacine M'Bengue, Xavier Blanchet, Kerstin Uhland, Martin Ungerer, Richard Brandl, Christian Weber, Natalie Elia, Reinhard Lorenz, Götz Münch, Wolfgang Siess
Platelet glycoprotein VI (GPVI) acts as a decisive collagen receptor in atherothrombosis. Besides collagen, injured atherosclerotic plaques expose tissue factor (TF) that triggers fibrin formation. Two recent studies reported that platelet GPVI also functions as fibrin receptor, which would importantly widen the mode of action of GPVI-targeted antithrombotic drugs. We studied the binding of two GPVI fusion proteins to fibrin under static and arterial flow conditions. Fibrin was prepared from purified fibrinogen or generated more physiologically from endogenous fibrinogen by coagulating plasma with thrombin...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29362366/platelet-subpopulations-remain-despite-strong-dual-agonist-stimulation-and-can-be-characterised-using-a-novel-six-colour-flow-cytometry-protocol
#10
Anna Linnea Södergren, Sofia Ramström
It is recognised that platelets respond differently to activation, where a subpopulation of platelets adopt a procoagulant phenotype while others are aggregatory. However, it has not been thoroughly tested whether these subpopulations will remain in maximally activated samples, or if they are merely a result of different platelet sensitivities to agonist activation. Here platelets were activated with gradually increasing concentrations of thrombin and/or the GPVI agonist cross-linked collagen-related peptide (CRP-XL)...
January 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29301754/maintenance-of-murine-platelet-homeostasis-by-the-kinase-csk-and-phosphatase-cd148
#11
Jun Mori, Zoltan Nagy, Giada Di Nunzio, Christopher W Smith, Mitchell J Geer, Rashid Al Ghaithi, Johanna P van Geffen, Silke Heising, Luke Boothman, Bibian M E Tullemans, Joao N Correia, Louise Tee, Marijke J E Kuijpers, Paul Harrison, Johan W M Heemskerk, Gavin E Jarvis, Alexander Tarakhovsky, Arthur Weiss, Alexandra Mazharian, Yotis A Senis
Src family kinases (SFKs) coordinate the initiating and propagating activation signals in platelets, but it remains unclear how they are regulated. Here, we show that ablation of C-terminal Src kinase (Csk) and receptor-like protein tyrosine-phosphatase CD148 in mice results in a dramatic increase in platelet SFK activity, demonstrating that these proteins are essential regulators of platelet reactivity. Paradoxically, Csk/CD148-deficient mice exhibit reduced in vivo and ex vivo thrombus formation and increased bleeding following injury rather than a prothrombotic phenotype...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29297508/current-and-future-antiplatelet-therapies-emphasis-on-preserving-haemostasis
#12
REVIEW
James D McFadyen, Mathieu Schaff, Karlheinz Peter
Antiplatelet drugs, such as aspirin, P2Y12 antagonists, and glycoprotein (GP) IIb/IIIa inhibitors, have proved to be successful in reducing the morbidity and mortality associated with arterial thrombosis. These agents are, therefore, the cornerstone of therapy for patients with acute coronary syndromes. However, these drugs all carry an inherent risk of bleeding, which is associated with adverse cardiovascular outcomes and mortality. Thus, the potential benefits of more potent, conventional antiplatelet drugs are likely be offset by the increased risk of bleeding...
March 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29296791/fibrin-and-d-dimer-bind-to-monomeric-gpvi
#13
Marie-Blanche Onselaer, Alexander T Hardy, Clare Wilson, Ximena Sanchez, Amir K Babar, Jeanette L C Miller, Callum N Watson, Stephanie K Watson, Arkadiusz Bonna, Helen Philippou, Andrew B Herr, Diego Mezzano, Robert A S Ariëns, Steve P Watson
Fibrin has recently been shown to activate platelets through the immunoglobulin receptor glycoprotein VI (GPVI). In the present study, we show that spreading of human platelets on fibrin is abolished in patients deficient in GPVI, confirming that fibrin activates human platelets through the immunoglobulin receptor. Using a series of proteolytic fragments, we show that D-dimer, but not the E fragment of fibrin, binds to GPVI and that immobilized D-dimer induces platelet spreading through activation of Src and Syk tyrosine kinases...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295843/gpvi-signaling-is-compromised-in-newly-formed-platelets-after-acute-thrombocytopenia-in-mice
#14
Shuchi Gupta, Deya Cherpokova, Markus Spindler, Martina Morowski, Markus Bender, Bernhard Nieswandt
At sites of vascular injury, exposed subendothelial collagens trigger platelet activation and thrombus formation by interacting with the immunoreceptor tyrosine-based activation motif (ITAM)-coupled glycoprotein VI (GPVI) on the platelet surface. Platelets are derived from the cytoplasm of megakaryocytes (MKs), which extend large proplatelets into bone marrow (BM) sinusoids that are then released into the bloodstream, where final platelet sizing and maturation occurs. The mechanisms that prevent activation of MKs and forming proplatelets in the collagen-rich BM environment remain largely elusive...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29258493/antiplatelet-mechanism-of-an-herbal-mixture-prepared-from-the-extracts-of-phyllostachys-pubescens-leaves-and-prunus-mume-fruits
#15
Eunjung Son, Seung-Hyung Kim, Won-Kyung Yang, Dong-Seon Kim, Jimin Cha
BACKGROUND: Bamboo (Phyllostachys pubescens) leaves and Japanese apricot (Mume fructus) fruit are traditionally recognized to be safe herbs broadly used for food and medicinal purposes in Southeast Asia. Our group previously explored their antiplatelet effects. This study was designed to confirm inhibition effects of PM21 (a 2:1 mixture of bamboo leaf extract and Japanese apricot fruit extract) on platelet aggregation and evaluate its potency to use as an herbal remedy to prevent and/or treat the diseases caused by platelet aggregation and thrombus formation...
December 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29242851/in-depth-ptdins-3-4-5-p-3-signalosome-analysis-identifies-dapp1-as-a-negative-regulator-of-gpvi-driven-platelet-function
#16
Tom N Durrant, James L Hutchinson, Kate J Heesom, Karen E Anderson, Len R Stephens, Phillip T Hawkins, Aaron J Marshall, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI3K) isoforms play important roles in platelet priming, activation, and stable thrombus formation. Class I PI3Ks predominantly regulate cell function through their catalytic product, the signaling phospholipid phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3 ], which coordinates the localization and/or activity of a diverse range of binding proteins. Notably, the complete repertoire of these class I PI3K effectors in platelets remains unknown, limiting mechanistic understanding of class I PI3K-mediated control of platelet function...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29237371/genetic-variability-of-src-family-kinases-and-its-association-with-platelet-hyperreactivity-and-clinical-outcomes-a-systematic-review
#17
Lukasz Milanowski, Fazila Rasul, Sylwia Natalia Gajda, Ceren Eyileten, Jolanta M Siller-Matula, Marek Postula
BACKGROUND: Platelet hyperactivity has been implicated many cardiovascular (CV) events such as ischemic stroke, myocardial infarction and CV death. Genetic variability of platelet receptors has been shown to impact Src family kinases (SFKs) activation and in turn influence platelet activation. SFKs are important signal transmitters in platelets, interacting with several receptors as GPIIB/IIIa, GPIb, PEAR 1, GPIa, GPVI, PECAM and CD148. METHODS: In this review, we focused on genetic variants of platelet receptors whose signals are transmitted mainly by SFKs and may be associated with clinical manifestations of platelet hyperactivation like MI or IS...
December 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29215030/traf3-negatively-regulates-platelet-activation-and-thrombosis
#18
Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li
CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29210180/platelet-collagen-receptor-glycoprotein-vi-dimer-recognizes-fibrinogen-and-fibrin-through-their-d-domains-contributing-to-platelet-adhesion-and-activation-during-thrombus-formation
#19
I Induruwa, M Moroi, A Bonna, J-D Malcor, J-M Howes, E A Warburton, R W Farndale, S M Jung
Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin interaction supports spreading, activation and adhesion involving αIIbβ3. SUMMARY: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin...
February 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29206067/oligomeric-and-fibrillar-amyloid-beta-42-induce-platelet-aggregation-partially-through-gpvi
#20
O Elaskalani, I Khan, M Morici, C Matthysen, M Sabale, R N Martins, G Verdile, P Metharom
The effects of the Alzheimer's disease (AD)-associated Amyloid-β (Aβ) peptides on platelet aggregation have been previously assessed, but most of these studies focused on Aβ40 species. It also remains to be determined which distinct forms of Aβ peptides exert differential effects on platelets. In AD, oligomeric Aβ42 species is widely thought to be a major contributor to the disease pathogenesis. We, therefore, examine the ability of oligomeric and fibrillary Aβ42 to affect platelet aggregation. We show that both forms of Aβ42 induced significant platelet aggregation and that it is a novel ligand for the platelet receptor GPVI...
December 5, 2017: Platelets
keyword
keyword
2613
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"