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Platelet integrin

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https://www.readbyqxmd.com/read/28441661/defective-platelet-activation-and-bleeding-complications-upon-cholestasis-in-mice
#1
Nina Sarah Gowert, Meike Klier, Maria Reich, Friedrich Reusswig, Lili Donner, Verena Keitel, Dieter Häussinger, Margitta Elvers
BACKGROUND/AIMS: Platelets are essential mediators of hemostasis to avoid excessive blood loss. Cirrhosis and chronic liver diseases are characterized by alterations in hemostasis. Alterations in the secondary hemostasis have been well studied, while defects in primary hemostasis, especially the consequences of cholestatic liver disease on platelet function are not well defined. METHODS: After bile duct ligation (BDL) platelet activation and thrombus formation were analyzed in mice...
April 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28441050/comparison-of-platelet-function-and-viscoelastic-test-results-between-healthy-dogs-and-dogs-with-naturally-occurring-chronic-kidney-disease
#2
Alicia Dudley, Julie K Byron, Mary Jo Burkhard, Emma Warry, Julien Guillaumin
OBJECTIVE To compare platelet function and viscoelastic test results between healthy dogs and dogs with chronic kidney disease (CKD) to assess whether dogs with CKD have platelet dysfunction and altered blood coagulation. ANIMALS 10 healthy control dogs and 11 dogs with naturally occurring CKD. PROCEDURES Blood and urine were collected once from each dog for a CBC, serum biochemical analysis, urinalysis, and determination of the urine protein-to-creatinine ratio, prothrombin time, activated partial thromboplastin time, plasma fibrinogen concentration, and antithrombin activity...
May 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28432753/identification-of-indothiazinone-as-a-natural-antiplatelet-agent
#3
Chansik Yang, Sugyeong Kwon, Se-Jong Kim, Minseon Jeong, Ji-Young Park, Dongeun Park, Soon Jun Hong, Jong-Wha Jung, Chungho Kim
Cardiovascular disease, which is caused by unregulated platelet aggregation, is one of the main causes of deaths worldwide. Many studies have focused on natural products with antiplatelet effects as a safe alternative therapy in order to prevent the disease. In this context, an in-house chemical library was screened to find natural products capable of inhibiting the interaction between platelet integrin αIIbβ3 and fibrinogen, which is an essential step in platelet aggregation. On the basis of the screening results, indothiazinone, an alkaloid found in microbial cultures, was identified as a potential antiplatelet agent...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28431006/regulation-of-oxidized-platelet-lipidome-implications-for-coronary-artery-disease
#4
Madhumita Chatterjee, Dominik Rath, Jörg Schlotterbeck, Johannes Rheinlaender, Britta Walker-Allgaier, Nada Alnaggar, Monika Zdanyte, Iris Müller, Oliver Borst, Tobias Geisler, Tilman E Schäffer, Michael Lämmerhofer, Meinrad Gawaz
Aims: Hyperlipidaemia enhances susceptibility to thrombosis, while platelet oxidixed LDL (oxLDL) binding in acute coronary syndrome (ACS) correlates with activation status. This study explores the platelet lipidome in symptomatic coronary artery disease (CAD) patients and the functional consequences of the chemokine CXCL12 and its receptors CXCR-4/-7 on lipid uptake in platelets. Methods and results: Platelet-oxLDL detected by flow cytometry was enhanced (P = 0...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28428218/gain-of-function-mutation-in-filamin-a-potentiates-platelet-integrin-%C3%AE-iib%C3%AE-3-activation
#5
Eliane Berrou, Frédéric Adam, Marilyne Lebret, Virginie Planche, Patricia Fergelot, Odile Issertial, Isabelle Coupry, Jean-Claude Bordet, Paquita Nurden, Dominique Bonneau, Estelle Colin, Cyril Goizet, Jean-Philippe Rosa, Marijke Bryckaert
OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28428216/maturation-of-platelet-function-during-murine-fetal-development-in-vivo
#6
Andreas Margraf, Claudia Nussbaum, Ina Rohwedder, Sarah Klapproth, Angela R M Kurz, Annamaria Florian, Volker Wiebking, Joachim Pircher, Monika Pruenster, Roland Immler, Steffen Dietzel, Ludmila Kremer, Friedemann Kiefer, Markus Moser, Andreas W Flemmer, Elizabeth Quackenbush, Ulrich H von Andrian, Markus Sperandio
OBJECTIVE: Platelet function has been intensively studied in the adult organism. However, little is known about the function and hemostatic capacity of platelets in the developing fetus as suitable in vivo models are lacking. APPROACH AND RESULTS: To examine fetal platelet function in vivo, we generated a fetal thrombosis model and investigated light-/dye-induced thrombus formation by intravital microscopy throughout gestation. We observed that significantly less and unstable thrombi were formed at embryonic day (E) 13...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28427432/anti-human-platelet-antigen-hpa-1a-antibodies-may-affect-trophoblast-functions-crucial-for-placental-development-a-laboratory-study-using-an-in-vitro-model
#7
Mariana Eksteen, Gøril Heide, Heidi Tiller, Yan Zhou, Nora Hersoug Nedberg, Inigo Martinez-Zubiaurre, Anne Husebekk, Bjørn R Skogen, Tor B Stuge, Mette Kjær
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies...
April 21, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28417457/effects-of-riboflavin-and-ultraviolet-light-treatment-on-platelet-thrombus-formation-and-thrombus-stability-on-collagen
#8
Chikahiro Terada, Masayuki Shiba, Tadashi Nagai, Masahiro Satake
BACKGROUND: Pathogen reduction technologies (PRTs) are considered for the implementation of safer platelet (PLT) transfusion. PRT treatment involves the addition of a photosensitizer to a blood component followed by ultraviolet (UV) light irradiation. However, the effects of PRT treatment on PLT thrombus formation and thrombus stability have not been satisfactorily clarified. STUDY DESIGN AND METHODS: Leukoreduced PLT concentrates (PCs) were treated with riboflavin and UV light (Mirasol PRT)...
April 17, 2017: Transfusion
https://www.readbyqxmd.com/read/28411253/a-new-path-to-platelet-production-through-matrix-sensing
#9
Vittorio Abbonante, Christian Andrea Di Buduo, Cristian Gruppi, Carmelo De Maria, Elise Spedden, Aurora De Acutis, Cristian Staii, Mario Raspanti, Giovanni Vozzi, David Kaplan, Francesco Moccia, Katya Ravid, Alessandra Balduini
Megakaryocytes in the bone marrow are immersed in a network of extracellular matrix (ECM) components that regulate platelet release into the circulation. Combining biological and bioengineering approaches, we found that the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechano-sensitive ion channel, is induced upon megakaryocyte adhesion on softer matrices. This response promoted platelet production by triggering a cascade of events that lead to calcium influx, β1 integrin activation and internalization, and Akt phosphorylation, responses not found on stiffer matrices...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28409495/antiplatelet-and-anti-proliferative-action-of-disintegrin-from-echis-multisquamatis-snake-venom
#10
Volodymyr Chernyshenko, Natalia Petruk, Darya Korolova, Ludmila Kasatkina, Olha Gornytska, Tetyana Platonova, Tamara Chernyshenko, Andriy Rebriev, Olena Dzhus, Liudmyla Garmanchuk, Eduard Lugovskoy
AIM: To purify the platelet aggregation inhibitor from Echis multisquamatis snake venom (PAIEM) and characterize its effect on platelet aggregation and HeLa cell proliferation. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) were used for PAIEM identification. Platelet aggregation in the presence of PAIEM was studied on aggregometer Solar-AP2110. The changes of shape and granularity of platelets in the presence of PAIEM were studied on flow cytometer COULTER EPICS XL, and degranulation of platelets was estimated using spectrofluorimetry...
April 14, 2017: Croatian Medical Journal
https://www.readbyqxmd.com/read/28406726/role-of-heterotrimeric-g-proteins-in-platelet-activation-and-clot-formation-in-platelets-treated-with-integrin-%C3%AE-iib%C3%AE-3-inhibitor
#11
Ivan Budnik, Boris Shenkman, Hagit Hauschner, Isaac Zilinsky, Naphtali Savion
Mechanisms of platelet activation are triggered by thrombin, adenosine diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which induce signaling via heterotrimeric Gαq, Gαi, and Gα12/13 proteins. We have undertaken a study addressing the contribution of these G proteins to platelet activation and clot formation in the presence of eptifibatide, thus excluding outside-in signaling provided by integrin αIIbβ3-fibrinogen engagement. Selective and combined activation of the G proteins was achieved by using combinations of platelet agonists and inhibitors...
April 13, 2017: Platelets
https://www.readbyqxmd.com/read/28404545/doxepin-inhibits-gpvi-dependent-platelet-ca-2-signaling-and-collagen-dependent-thrombus-formation
#12
Sascha Geue, Britta Walker-Allgaier, Daniela Eißler, Roland Tegtmeyer, Malte Schaub, Florian Lang, Meinrad Gawaz, Oliver Borst, Patrick Münzer
Platelet adhesion, activation and aggregation are essential for primary haemostasis, but are also critically involved in the development of acute arterial thrombotic occlusion. Stimulation of the collagen receptor glyocoprotein VI (GPVI) leads to PLCγ-dependent IP3 production with subsequent platelet activation, due to increased intracellular calcium concentration ([Ca(2+)]i). Although it has been described that tricyclic antidepressants potentially impair platelet activation, nothing is hitherto known about potential effects of the tricyclic antidepressant doxepin on platelet Ca(2+) signaling and thrombus formation...
April 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28399159/effects-of-the-rgd-loop-and-c-terminus-of-rhodostomin-on-regulating-integrin-%C3%AE-iib%C3%AE-3-recognition
#13
Yao-Tsung Chang, Jia-Hau Shiu, Chun-Hao Huang, Yi-Chun Chen, Chiu-Yueh Chen, Yung-Sheng Chang, Woei-Jer Chuang
Rhodostomin (Rho) is a medium disintegrin containing a 48PRGDMP motif. We here showed that Rho proteins with P48A, M52W, and P53N mutations can selectively inhibit integrin αIIbβ3. To study the roles of the RGD loop and C-terminal region in disintegrins, we expressed Rho 48PRGDMP and 48ARGDWN mutants in Pichia pastoris containing 65P, 65PR, 65PRYH, 65PRNGLYG, and 65PRNPWNG C-terminal sequences. The effect of C-terminal region on their integrin binding affinities was αIIbβ3 > αvβ3 ≥ α5β1, and the 48ARGDWN-65PRNPWNG protein was the most selective integrin αIIbβ3 mutant...
2017: PloS One
https://www.readbyqxmd.com/read/28395882/should-studies-on-glanzmann-thrombasthenia-not-be-telling-us-more-about-cardiovascular-disease-and-other-major-illnesses
#14
REVIEW
Alan T Nurden
Glanzmann thrombasthenia (GT) is a rare inherited bleeding disorder caused by loss of αIIbβ3 integrin function in platelets. Most genetic variants of β3 also affect the widely expressed αvβ3 integrin. With brief mention of mouse models, I now look at the consequences of disease-causing ITGA2B and ITGB3 mutations on the non-hemostatic functions of platelets and other cells. Reports of arterial thrombosis in GT patients are rare, but other aspects of cardiovascular disease do occur including deep vein thrombosis and congenital heart defects...
April 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28389621/fluid-shear-induced-cathepsin-b-release-in-the-control-of-mac1-dependent-neutrophil-adhesion
#15
Michael L Akenhead, Shunichi Fukuda, Geert W Schmid-Schönbein, Hainsworth Y Shin
There is compelling evidence that circulatory hemodynamics prevent neutrophil activation, including adhesion to microvessels, in the microcirculation. However, the underlying mechanism or mechanisms by which that mechanoregulation occurs remain unresolved. Here, we report evidence that exposure to fluid shear stress (FSS) promotes neutrophils to release cathepsin B (ctsB) and that this autocrine regulatory event is antiadhesive for neutrophils on endothelial surfaces through Mac1-selective regulation. We used a combined cell-engineering and immunocytochemistry approach to find that ctsB was capable of cleaving Mac1 integrins on neutrophils and demonstrated that this proteolysis alters their adhesive functions...
April 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28370162/simultaneous-human-platelet-antigen-genotyping-and-detection-of-novel-single-nucleotide-polymorphisms-by-targeted-next-generation-sequencing
#16
Sue Davey, Cristina Navarrete, Colin Brown
BACKGROUND: Twenty-nine human platelet antigen systems have been described to date, but the majority of current genotyping methods are restricted to the identification of those most commonly associated with alloantibody production in a clinical context. This can result in a protracted investigation if causative human platelet antigens are rare or novel. A targeted next-generation sequencing approach was designed to detect all known human platelet antigens with the additional capability of identifying novel mutations in the encoding genes...
March 28, 2017: Transfusion
https://www.readbyqxmd.com/read/28358707/polymorphisms-of-platelet-glycoprotein-receptors-and-cell-adhesion-molecules-in-fetuses-with-fetal-growth-restriction-and-their-mothers-as-detected-with-pyrosequencing
#17
Maria Simou, Evaggelia Kouskouni, Nikolaos Vitoratos, Emmanuel Economou, George Creatsas
BACKGROUND: Vascular thrombotic tendency may lead to fetal growth restriction (FGR). Altered platelet function and genetic heterogeneity may play a role in this procedure. We investigated whether maternal or fetal genotypic frequencies of genes polymorphisms for certain platelet receptor and cell adhesion molecules are altered in FGR. MATERIALS AND METHODS: We compared the maternal and fetal genotypic frequencies of single nucleotide polymorphisms (SNPs) in four genes coding for platelet receptors and cell adhesion molecules [integrin alpha subunit 2 (ITGA2)C807T, integrin subunit beta 3(ITGB3) T1565C, platelet cell adhesion protein 1 (PECAM1) CTG-GTG and selectin P(SELP)A/C]...
March 2017: In Vivo
https://www.readbyqxmd.com/read/28351192/synergistic-effect-of-peptide-inhibitors-derived-from-the-extracellular-and-intracellular-domain-of-%C3%AE-iib-subunit-of-integrin-%C3%AE-iib%C3%AE-3-on-platelet-activation-and-aggregation
#18
Alexia V Gkourogianni, Klytaimnistra Kiouptsi, Vassiliki Koloka, Vassilios Moussis, Vassilios Tsikaris, Christilla Bachelot-Loza, Demokritos C Tsoukatos
αIIbβ3, the major platelet integrin, plays a central role in hemostasis and thrombosis. Upon platelet activation, conformation of αIIbβ3 changes and allows fibrinogen binding and, subsequently, platelet aggregation. It was previously shown that a lipid-modified platelet permeable peptide, which corresponds to the intracellular acidic membrane distal sequence (1000)LEEDDEEGE(1008) of αIIb (pal-K-LEEDDEEGE or pal-K-1000-1008), inhibits thrombin-induced human platelet aggregation, by inhibiting talin association with the integrin...
March 29, 2017: Platelets
https://www.readbyqxmd.com/read/28336561/mice-lacking-the-inhibitory-collagen-receptor-lair-1-exhibit-a-mild-thrombocytosis-and-hyperactive-platelets
#19
Christopher W Smith, Steven G Thomas, Zaher Raslan, Pushpa Patel, Maxwell Byrne, Marie Lordkipanidzé, Danai Bem, Linde Meyaard, Yotis A Senis, Steve P Watson, Alexandra Mazharian
OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif-containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28314136/platelet-microparticle-inspired-clot-responsive-nanomedicine-for-targeted-fibrinolysis
#20
Christa L Pawlowski, Wei Li, Michael Sun, Kavya Ravichandran, DaShawn Hickman, Clarissa Kos, Gurbani Kaur, Anirban Sen Gupta
Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger...
June 2017: Biomaterials
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