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https://www.readbyqxmd.com/read/28164654/expression-of-platelet-collagen-receptor-glycoprotein-vi-in-coronary-heart-disease-interaction-between-platelets-and-endothelial-cells
#1
Jian Shi, Ning Zhu, Jiwen Wang, Yu Wang, Zhaohong Geng, Suya Gao, Zhongyan Li
BACKGROUND: 1) To investigate the expression of platelet collagen receptor glycoprotein VI (GPVI) on the surface of platelets in patients with coronary heart disease (CHD). 2) To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of endothelial cells after exposure to subjects' platelets. METHODS: Platelets were extracted from blood samples of 97 subjects including 43 with acute coronary syndrome (ACS), 21 with stable angina pectoris (SAP), and 33 serving as controls in which CHD was excluded...
July 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28155721/computer-prediction-of-paratope-on-antithrombotic-antibody-10b12-and-epitope-on-platelet-glycoprotein-vi-via-molecular-dynamics-simulation
#2
Wenping Liu, Guangjian Liu, Huiyun Zhou, Xiang Fang, Ying Fang, Jianhua Wu
BACKGROUND: Interaction between immunoglobulin-like receptor glycoprotein VI (GPVI) and collagen plays a central role in platelet activation and sequent firm adhesion. Of various antithrombotic agents targeting GPVI, antibody 10B12 is of great potential to block the GPVI-collagen interaction, but less is known about 10B12 paratope and GPVI epitope. METHODS: Along the pathway in the computer strategy presented in our previous work, the 10B12/GPVI complex model was constructed through homology modeling and rigid-body docking, and the molecular dynamics (MD) simulation was used to detect the paratope residues on 10B12 and their partners on GPVI...
December 28, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28102731/microfluidic-whole-blood-testing-of-platelet-response-to-pharmacological-agents
#3
Ruizhi Li, Tilo Grosser, Scott L Diamond
Platelets present a number of intracellular and transmembrane targets subject to pharmacological modulation, either for cardiovascular disease reduction or as an unintended drug response. Microfluidic devices allow human blood to clot on a defined surface under controlled hemodynamic and pharmacological conditions. The potencies of a number of antiplatelet and anticancer drugs have been tested with respect to platelet deposition on collagen under flow. Inhibitors of cyclooxygenase-1 (COX-1) reduce platelet deposition, either when added ex vivo to blood or ingested orally by patients prior to testing...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28058806/clustering-of-glycoprotein%C3%A2-vi-gpvi-dimers-upon-adhesion-to-collagen-as-a-mechanism-to-regulate-gpvi-signaling-in-platelets
#4
N S Poulter, A Y Pollitt, D M Owen, E E Gardiner, R K Andrews, H Shimizu, D Ishikawa, D Bihan, R W Farndale, M Moroi, S P Watson, S M Jung
Essentials Dimeric high-affinity collagen receptor glycoprotein VI (GPVI) is present on resting platelets. Spatio-temporal organization of platelet GPVI-dimers was evaluated using advanced microscopy. Upon platelet adhesion to collagenous substrates, GPVI-dimers coalesce to form clusters. Clustering of GPVI-dimers may increase avidity and facilitate platelet activation SUMMARY: Background Platelet glycoprotein VI (GPVI) binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28032533/tetraspanin-tspan9-regulates-platelet-collagen-receptor-gpvi-lateral-diffusion-and-activation
#5
Elizabeth J Haining, Alexandra L Matthews, Peter J Noy, Hanna M Romanska, Helen J Harris, Jeremy Pike, Martina Morowski, Rebecca L Gavin, Jing Yang, Pierre-Emmanuel Milhiet, Fedor Berditchevski, Bernhard Nieswandt, Natalie S Poulter, Steve P Watson, Michael G Tomlinson
The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28004756/alteration-of-platelet-gpvi-signaling-in-st-elevation-myocardial-infarction-patients-demonstrated-by-a-combination-of-proteomic-biochemical-and-functional-approaches
#6
Paula Vélez, Raymundo Ocaranza-Sánchez, Diego López-Otero, Lilian Grigorian-Shamagian, Isaac Rosa, Esteban Guitián, José María García-Acuña, José Ramón González-Juanatey, Ángel García
The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide)...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27999100/platelet-hyperreactivity-in-diabetes-focus-on-gpvi-signaling-are-useful-drugs-already-available
#7
Jane F Arthur, Karin Jandeleit-Dahm, Robert K Andrews
Adults with diabetes are 2-4 times more likely to suffer from heart disease or ischemic stroke than adults without diabetes, yet standard antiplatelet therapy, which is the cornerstone for primary and secondary prevention of cardiovascular disease, fails in many patients with diabetes. Three independent but often interrelated variables that contribute to platelet hyperreactivity-high blood glucose, oxidative stress, and elevated vascular shear forces-coexist in patients with diabetes, creating a perilous concurrence of risk factors for cardiovascular events...
January 2017: Diabetes
https://www.readbyqxmd.com/read/27996269/novel-glycoprotein-vi-antagonists-as-antithrombotics-synthesis-biological-evaluation-and-molecular-modeling-studies-on-2-3-disubstituted-tetrahydropyrido-3-4-b-indoles
#8
Shome S Bhunia, Ankita Misra, Imran A Khan, Stuti Gaur, Manish Jain, Surendra Singh, Aaruni Saxena, Thomas Hohlfield, Madhu Dikshit, Anil K Saxena
The development of small molecule inhibitors targeting GPVI has promising therapeutic role, as they inhibit arterial thrombosis with limited risk of bleeding. Among the compounds showing in vivo antithrombotic activity, the most active compound 6b (ED50 = 28.36 μmol/kg po in mice) showed improved inhibition for collagen (IC50 = 6.7 μM), CRP-XL (IC50 = 53.5 μM), and convulxin (CVX) (IC50 = 5.7 μM) mediated platelet aggregation as compared to losartan (LOS) (collagen, IC50 = 10.4 μM; CRP-XL, IC50 = 158 μM; CVX, IC50 = 11 μM) than any of its enantiomers S (6c) (collagen, IC50 = 25...
December 20, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27965959/a-novel-antithrombotic-mechanism-mediated-by-the-receptors-of-the-kallikrein-kinin-and-renin-angiotensin-systems
#9
REVIEW
Alvin H Schmaier
The contact activation (CAS) and kallikrein/kinin (KKS) systems regulate thrombosis risk in two ways. First, the CAS influences contact activation-induced factor XI activation and thrombin formation through the hemostatic cascade. Second, prekallikrein (PK) and bradykinin of the KKS regulate expression of three vessel wall G-protein-coupled receptors, the bradykinin B2 receptor (B2R), angiotensin receptor 2, and Mas to influence prostacyclin formation. The degree of intravascular prostacyclin formation inversely regulates intravascular thrombosis risk...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27924212/combined-administration-of-the-gpvi-fc-fusion-protein-revacept-with-low-dose-thrombolysis-in-the-treatment-of-stroke
#10
Andreas Reimann, Zhongmin Li, Silvia Goebel, Julia Fassbender, Hans-Peter Holthoff, Meinrad Gawaz, Götz Münch, Martin Ungerer
BACKGROUND: Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) remains the only approved medication for acute ischemic stroke, but incurs significant bleeding risks. Therefore, approaches to combine lower doses of thrombolytic therapy with other effective drugs aim at improving efficacy and reducing bleeding rates. We examined the safety and therapeutic effects of various dosings of rtPA, either alone or combined with glycoprotein VI-Fc fusion protein (GPVI-Fc, Revacept) on experimental stroke in mice...
January 2016: Heart International
https://www.readbyqxmd.com/read/27896950/ppar%C3%AE-agonists-negatively-regulate-%C3%AE-iib%C3%AE-3-integrin-outside-in-signaling-and-platelet-function-through-up-regulation-of-protein-kinase-a-activity
#11
A J Unsworth, N Kriek, A P Bye, K Naran, T Sage, G D Flora, J M Gibbins
: Essentials peroxisome proliferator-activated receptor γ (PPARγ) agonists inhibit platelet function. PPARγ agonists negatively regulate outside-in signaling via integrin αIIbβ3. PPARγ agonists disrupt the interaction of Gα13 with integrin β3. This is attributed to an upregulation of protein kinase A activity. SUMMARY: Background Agonists for the peroxisome proliferator-activated receptor (PPARγ) have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists...
November 29, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27818280/gpvi-and-thromboxane-receptor-on-platelets-promote-proinflammatory-macrophage-phenotypes-during-cutaneous%C3%A2-inflammation
#12
Sandra Pierre, Bona Linke, Jing Suo, Neda Tarighi, Domenico Del Turco, Dominique Thomas, Nerea Ferreiros, David Stegner, Stefanie Frölich, Marco Sisignano, Sascha Meyer Dos Santos, Natasja deBruin, Rolf M Nüsing, Thomas Deller, Bernhard Nieswandt, Gerd Geisslinger, Klaus Scholich
Platelets are well known for their role in hemostasis but are also increasingly recognized for their supporting role in innate immune responses. Here, we studied the role of platelets in the development of peripheral inflammation and found that platelets colocalize with macrophages in the inflamed tissue outside of blood vessels in different animal models for cutaneous inflammation. Collagen-treatment of macrophages isolated from paws during zymosan-induced inflammation induced thromboxane synthesis through the platelet-expressed collagen receptor glycoprotein VI...
November 3, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27778530/gpvi-modulation-during-platelet-activation-and-storage-its-expression-levels-and-ectodomain-shedding-compared-to-markers-of-platelet-storage-lesion
#13
Ehteramolsadat Hosseini, Mehran Ghasemzadeh, Fatemeh Nassaji, Zeynab Pirmohammad Jamaat
Platelet storage is associated with deleterious changes leading to the loss of platelet reactivity and response. During storage, platelets experience increased expression and shedding of P-selectin and CD40L as specific markers of platelet activation, whereas GPIbα decreases due to ectodomain shedding. As an important adhesive receptor, GPVI contributes significantly to thrombus formation while its expression and shedding levels during storage of platelet products have not been well characterized yet. This study investigated the modulation of GPVI during platelet storage...
October 25, 2016: Platelets
https://www.readbyqxmd.com/read/27766315/cross-linking-gpvi-fc-by-anti-fc-antibodies-potentiates-its-inhibition-of%C3%A2-atherosclerotic-plaque-and-collagen-induced-platelet-activation
#14
Janina Jamasbi, Remco T A Megens, Mariaelvy Bianchini, Kerstin Uhland, Götz Münch, Martin Ungerer, Shachar Sherman, Alexander Faussner, Richard Brandl, Christine John, Johannes Buchner, Christian Weber, Reinhard Lorenz, Natalie Elia, Wolfgang Siess
To enhance the antithrombotic properties of recombinant glycoprotein VI fragment crystallizable (GPVI-Fc), the authors incubated GPVI-Fc with anti-human Fc antibodies to cross-link the Fc tails of GPVI-Fc. Cross-linking potentiated the inhibition of human plaque- and collagen-induced platelet aggregation by GPVI-Fc under static and flow conditions without increasing bleeding time in vitro. Cross-linking with anti-human-Fc Fab2 was even superior to anti-human-Fc immunoglobulin G (IgG). Advanced optical imaging revealed a continuous sheath-like coverage of collagen fibers by cross-linked GPVI-Fc complexes...
April 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/27766055/platelets-and-platelet-adhesion-molecules-novel-mechanisms-of-thrombosis-and-anti-thrombotic-therapies
#15
REVIEW
Xiaohong Ruby Xu, Naadiya Carrim, Miguel Antonio Dias Neves, Thomas McKeown, Tyler W Stratton, Rodrigo Matos Pinto Coelho, Xi Lei, Pingguo Chen, Jianhua Xu, Xiangrong Dai, Benjamin Xiaoyi Li, Heyu Ni
Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27766044/anti-thrombotic-agents-derived-from-snake-venom-proteins
#16
REVIEW
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27761580/decreased-platelet-reactivity-in-patients-with-cancer-is-associated-with-high-risk-of-venous-thromboembolism-and-poor-prognosis
#17
Julia Riedl, Alexandra Kaider, Christine Marosi, Gerald W Prager, Beate Eichelberger, Alice Assinger, Ingrid Pabinger, Simon Panzer, Cihan Ay
Platelets are suggested to play a crucial role in cancer progression and the prothrombotic state of cancer patients. Here, we aimed to examine the activation status of platelets in cancer patients and investigate their association with risk of death and occurrence of venous thromboembolism (VTE) in a prospective observational cohort study. We measured platelet surface P-selectin, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregate (MPA) formation in vivo and platelet response to ex vivo stimulation with agonists of protease-activated receptor (PAR) -1, -4, and GPVI, by whole blood flow cytometry, before beginning of chemotherapy and repeatedly during the first six months thereafter (total number of samples analysed: 230)...
October 20, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27753514/clinical-significance-of-receptor-shedding-platelet-gpvi-as-an-emerging-diagnostic-and-therapeutic-tool
#18
Madhumita Chatterjee, Meinrad Gawaz
Platelet membrane bedecked with a wide array of receptors offers a platform to regulate platelet responsiveness, thrombotic propensity, inflammatory disposition, and immune reactivity under diverse pathophysiological conditions. Ectopic proteolytic cleavage of such receptors irreversibly inactivates receptor-mediated intracellular signaling governing cellular functions, further releases soluble fragments into circulation which might modulate functions of target cells. Glycoprotein VI-(GPVI) is a membrane glycoprotein expressed in platelets and megakaryocytes...
October 18, 2016: Platelets
https://www.readbyqxmd.com/read/27716777/thioredoxin-inhibitors-attenuate-platelet-function-and-thrombus-formation
#19
Clive Metcalfe, Anjana Ramasubramoni, Giordano Pula, Matthew T Harper, Stuart J Mundell, Carmen H Coxon
Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis...
2016: PloS One
https://www.readbyqxmd.com/read/27693274/anti-xa-oral-anticoagulants-inhibit-in-vivo-platelet-activation-by-modulating-glycoprotein-vi-shedding
#20
Pasquale Pignatelli, Daniele Pastori, Simona Bartimoccia, Danilo Menichelli, Tommasa Vicario, Cristina Nocella, Roberto Carnevale, Francesco Violi
Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40)...
September 28, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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