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Platelet integrin

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https://www.readbyqxmd.com/read/29617817/decreased-pecam1-mediated-tgf-%C3%AE-1-expression-in-the-mid-secretory-endometrium-in-women-with-recurrent-implantation-failure
#1
Feng Guo, Chenchen Si, Mingjuan Zhou, Jingwen Wang, Dan Zhang, Peter C K Leung, Bufang Xu, Aijun Zhang
STUDY QUESTION: Is recurrent implantation failure (RIF) associated with decreased expression of platelet and endothelial cell adhesion molecule 1 (PECAM1) and transforming growth factor β1 (TGF-β1) in the endometrium during the implantation window? SUMMARY ANSWER: The present study demonstrates that the expression of PECAM1 and TGF-β1 is significantly decreased in the mid-secretory endometrium in women with RIF, which may account for embryo implantation failure...
March 30, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29617175/maximum-likelihood-approach-suggests-positive-selection-in-platelet-integrin-%C3%AE-iib%C3%AE-3-in-mammalian-species
#2
Luís Bernardo Pina-Cabral, Miguel Carneiro, Begoña Criado, Pedro José Esteves
Platelet integrin αIIbβ3 is crucial for platelet aggregation. Although structural and functional characteristics of this protein have been extensively studied, the evolutionary pattern studies of this protein complex in mammals are scarce. Here, we addressed this question using maximum likelihood approaches to identify codons that are evolving under positive selection. Likelihood of positive selection was estimated using CODEML implemented in PAML software applied to integrin αIIbβ3 derived from nucleotide sequences of 10 different mammalian species...
April 4, 2018: Platelets
https://www.readbyqxmd.com/read/29615672/morphometric-analysis-of-spread-platelets-identifies-integrin-%C3%AE-iib-%C3%AE-3-specific-contractile-phenotype
#3
Sebastian Lickert, Simona Sorrentino, Jan-Dirk Studt, Ohad Medalia, Viola Vogel, Ingmar Schoen
Haemostatic platelet function is intimately linked to cellular mechanics and cytoskeletal morphology. How cytoskeletal reorganizations give rise to a highly contractile phenotype that is necessary for clot contraction remains poorly understood. To elucidate this process in vitro, we developed a morphometric screen to quantify the spatial organization of actin fibres and vinculin adhesion sites in single spread platelets. Platelets from healthy donors predominantly adopted a bipolar morphology on fibrinogen and fibronectin, whereas distinguishable, more isotropic phenotypes on collagen type I or laminin...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29605625/activation-of-soluble-guanylyl-cyclase-with-inhibition-of-multidrug-resistance-protein-inhibitor-4-mrp4-as-a-new-antiplatelet-therapy
#4
Camila B Mendes-Silverio, Caroline H Lescano, Tiago Zaminelli, Carolina Sollon, Gabriel F Anhê, Edson Antunes, Fabíola Z Mónica
The intracellular levels of cyclic GMP are controlled by its rate of formation through nitric oxide-mediated stimulation of soluble guanylate cyclase (sGC) and its degradation by phosphodiesterases. Multidrug resistance protein 4 (MRP4) expressed in human platelets pumps cyclic nucleotides out of cells. In search for new antiplatelet strategies, we tested the hypothesis that sGC activation concomitant with MRP4 inhibition confers higher antiplatelet efficacy compared with monotherapy alone. This study was undertaken to investigate the pharmacological association of the sGC activator BAY 60-2770 with the MRP4 inhibitor MK571 on human washed platelets...
March 29, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29599771/fresh-evidence-for-platelets-as-neuronal-and-innate-immune-cells-their-role-in-the-activation-differentiation-and-deactivation-of-th1-th17-and-tregs-during-tissue-inflammation
#5
REVIEW
Eugene D Ponomarev
Recent studies suggest that in addition to their common function in the regulation of thrombosis and hemostasis, platelets also contribute to tissue inflammation affecting adaptive immunity. Platelets have a number of pro-inflammatory and regulatory mediators stored in their α-granules and dense granules, which are promptly released at sites of inflammation or tissue injury. Platelet-derived mediators include cytokines (IL-1α, IL-1β, and TGFβ1), chemokines (CXCL4 and CCL3), immunomodulatory neurotransmitters (serotonin, dopamine, epinephrine, histamine, and GABA), and other low-molecular-weight mediators...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29569428/novel-assay-demonstrates-that-coronary-artery-disease-patients-have-heightened-procoagulant-platelet-response
#6
L Pasalic, E Wing-Lun, J K Lau, H Campbell, G J Pennings, E Lau, D Connor, Hai Po Helena Liang, D Muller, L Kritharides, P J Hogg, V M Chen
BACKGROUND: Procoagulant platelets are a subset of highly activated platelets with critical role in thrombin generation. Evaluation of their clinical utility in thrombotic disorders, such as coronary artery disease (CAD), has been thwarted by the lack of a sensitive and specific whole blood assay. OBJECTIVES: We developed a novel assay, utilizing the cell death marker, GSAO [(4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid], and the platelet activation marker, P-selectin, to identify procoagulant platelets in whole blood by flow cytometry...
March 22, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29567680/chronic-intake-of-the-selective-serotonin-reuptake-inhibitor-fluoxetine-enhances-atherosclerosis
#7
Martina Rami, Raquel Guillamat-Prats, Petteri Rinne, Melanie Salvermoser, Larisa Ring, Mariaelvy Bianchini, Xavier Blanchet, Remco T A Megens, Yvonne Döring, Barbara Walzog, Oliver Soehnlein, Christian Weber, Alexander Faussner, Sabine Steffens
OBJECTIVE: Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects of serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressant drugs, are controversial. In addition to blocking serotonin reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin (5-hydroxytryptamine [5-HT]) storage by inhibiting serotonin reuptake transporter-mediated uptake in platelets...
March 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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
#8
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
#9
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/29540687/compression-force-sensing-regulates-integrin-%C3%AE-iib-%C3%AE-3-adhesive-function-on-diabetic-platelets
#10
Lining Ju, James D McFadyen, Saheb Al-Daher, Imala Alwis, Yunfeng Chen, Lotte L Tønnesen, Sophie Maiocchi, Brianna Coulter, Anna C Calkin, Eric I Felner, Neale Cohen, Yuping Yuan, Simone M Schoenwaelder, Mark E Cooper, Cheng Zhu, Shaun P Jackson
Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin αIIb β3 on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion...
March 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29540475/leukocyte-integrin-mac-1-cd11b-cd18-%C3%AE-m-%C3%AE-2-cr3-acts-as-a-functional-receptor-for-platelet-factor-4
#11
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29527528/reflections-on-dry-eye-syndrome-treatment-therapeutic-role-of-blood-products
#12
REVIEW
Victor J Drew, Ching-Li Tseng, Jerard Seghatchian, Thierry Burnouf
Dry eye syndrome (DES) is a multifactorial, frequent, pathology characterized by deficient tear production or increased evaporation of tears and associated with ocular surface alteration and inflammation. It mostly affects, but not exclusively, older individuals and leads to varying degrees of discomfort and decreased quality of life. Although the typical treatments of DES rely on using artificial tears, polyunsaturated fatty acids, integrin antagonists, anti-inflammatory agents, or on performing punctal occlusion, recently, standardized blood-derived serum eye drops (SED) are generating much interest as a new physiological treatment option...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29496178/eisenia-bicyclis-brown-alga-modulates-platelet-function-and-inhibits-thrombus-formation-via-impaired-p-2-y-12-receptor-signaling-pathway
#13
Muhammad Irfan, Tae-Hyung Kwon, Bong-Sik Yun, Nyun-Ho Park, Man Hee Rhee
BACKGROUND AND PURPOSE: Sea weeds have been used since ancient times in Asian countries, especially in Korea, Japan, and China, as both edible sea vegetables and traditional medicinal tonics due to their health benefits. Eisenia bicyclis has been studied for anti-allergic and anti-cancer effects; however, its effects on the cardiovascular system, especially on platelet function, are yet to be explored. Therefore, we examined the effect of E. bicyclis on platelet function. STUDY DESIGN AND METHODS: E...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29490295/inhibition-of-collagen-related-peptide-induced-platelet-activation-and-apoptosis-by-ceritinib
#14
Hang Cao, Anja T Umbach, Rosi Bissinger, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma (tyrosine) kinase (ALK) inhibitor ceritinib triggers apoptosis of tumor cells and eryptosis of erythrocytes. Blood platelets may similarly enter a state resembling apoptosis, which could be triggered by activation with collagen related peptide (CRP). CRP-induced platelet apoptosis is characterized by cell membrane scrambling with phosphatidylserine exposure to the platelet surface and cell shrinkage, preceded by externalization of Ca2+ channel Orai1, increase of cytosolic Ca2+-activity ([Ca2+]i), formation of reactive oxygen species (ROS), and caspase activation...
February 23, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29470988/shear-dependent-fibrillogenesis-of-fibronectin-impact-of-platelet-integrins-and-actin-cytoskeleton
#15
Huong Nguyen, Khon Huynh, Volker R Stoldt
Soluble plasma fibronectin (Fn) with its inactive compact structure requires unfolding to assemble into active fibrils, which play a role in hemostasis and thrombosis. Fn fibril assembly involves Fn binding to cell receptors, biomechanical coupling of Fn to the cytoskeleton by integrins, exposure of self-assembly sites via contractile cell forces, and elongation of fibrils by Fn polymerization. In this report, we investigated the effect of platelet integrins and actin cytoskeleton on conformational changes of Fn induced by shear...
February 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29467183/the-search-for-new-antithrombotic-mechanisms-and-therapies-that-may-spare-hemostasis
#16
Edward F Plow, Yunmei Wang, Daniel I Simon
Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk, which increases morbidity and mortality. Nevertheless, there is emerging experimental evidence that suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby raising the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We summarize some recently emerging examples of agents with antithrombotic activities that seem to spare hemostasis...
February 21, 2018: Blood
https://www.readbyqxmd.com/read/29464566/conformational-equilibrium-of-human-platelet-integrin-investigated-by-three-dimensional-electron-cryo-microscopy
#17
Dorit Hanein, Niels Volkmann
Integrins are bidirectional transmembrane receptors that play central roles in hemostasis and arterial thrombosis. They have been subject to structural studies for many years, in particular using X-ray crystallography, nuclear magnetic resonance spectroscopy, and two-dimensional negative stain electron microscopy. Despite considerable progress, a full consensus on the molecular mechanism of integrin activation is still lacking. Three-dimensional reconstructions of full-length human platelet integrin αIIb β3 in lipid-bilayer nanodiscs obtained by electron cryo-microscopy and single-particle reconstruction have shed new light on the activation process...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29462793/the-human-platelet-antigen-1b-variant-of-%C3%AE-iib-%C3%AE-3-allosterically-shifts-the-dynamic-conformational-equilibrium-of-this-integrin-toward-the-active-state
#18
Giulia Pagani, Joana P V Pereira, Volker R Stoldt, Andreas Beck, Rüdiger E Scharf, Holger Gohlke
Integrins are heterodimeric cell-adhesion receptors comprising α and β subunits. The human platelet antigen-1 (HPA-1) polymorphism in αIIb β3 arises from a Leu→Pro exchange at residue 33 in the genu of the β3 subunit, resulting in Leu-33 (HPA-1a) or Pro-33 (HPA-1b) isoforms. Although clinical investigations have provided conflicting results, some studies have suggested that Pro-33 platelets exhibit increased thrombogenicity. Under flow-dynamic conditions, the Pro-33 variant displays prothrombotic properties, characterized by in-creased platelet adhesion, aggregate/thrombus formation, and outside-in signaling...
February 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29453194/comparison-of-generic-fluorescent-markers-for-detection-of-extracellular-vesicles-by-flow-cytometry
#19
Leonie de Rond, Edwin van der Pol, Chi M Hau, Zoltan Varga, Auguste Sturk, Ton G van Leeuwen, Rienk Nieuwland, Frank A W Coumans
BACKGROUND: Extracellular vesicles (EVs) in biofluids are potential biomarkers of disease. To explore the clinical relevance of EVs, a specific generic EV marker would be useful, one that does not require antibodies and binds to all EVs. Here we evaluated 5 commonly used generic markers for flow cytometry. METHODS: Flow cytometry (A60-Micro, Apogee) was used to evaluate the ability of the generic EV markers calcein acetoxymethyl ester, calcein acetoxymethyl ester violet, carboxyfluorescein succinimidyl ester (CFSE), 4-(2-[6-(dioctylamino)-2-naphthalenyl]ethenyl)-1-(3-sulfopropyl)pyridinium (di-8-ANEPPS), and lactadherin to stain EVs from MCF7 human breast adenocarcinoma cell line-conditioned culture medium [epithelial cell adhesion molecule positive (EpCAM + )] or platelet EVs from human plasma [integrin β3 positive (CD61 + )]...
February 16, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29446689/platelets-and-vascular-integrity
#20
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
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