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Chunyan Chen, Tingting Li, Yuchen Zhao, Yinfeng Qian, Xiaoyi Li, Xiangrong Dai, Dake Huang, Tianzhong Pan, Lanlan Zhou
Blood-brain barrier (BBB) disruption, thrombus formation and immune-mediated inflammation are important steps in the pathophysiology of cerebral ischemia-reperfusion injury but are still inaccessible to therapeutic interventions. Recent studies have provided increasing evidence that blocking of platelet glycoprotein (GP) receptor Ib might represent a novel target in treating acute ischemic stroke. This research was conducted to explore the therapeutic efficacy and potential mechanisms of GPIbα inhibitor (anfibatide) in a model of brain ischemia-reperfusion injury in mice...
March 2018: Brain, Behavior, and Immunity
Cécile Lavenu-Bombled, Corinne Guitton, Arnaud Dupuis, Marie-Jeanne Baas, Céline Desconclois, Marie Dreyfus, Renhao Li, Claudine Caron, Christian Gachet, Edith Fressinaud, François Lanza
Interaction between von Willebrand factor (VWF) and platelet GPIbα is required for primary haemostasis. Lack or loss-of-function in the ligand-receptor pair results in bleeding complications. Paradoxically, gain-of-function mutations in VWF or GPIbα also result in bleeding complications as observed in type 2B von Willebrand disease (VWD) and platelet-type- (PT-) VWD, respectively. A similar phenotype is observed with increased ristocetin-induced platelet agglutination and disappearance of the highest molecular weight multimers of VWF...
November 30, 2016: Thrombosis and Haemostasis
Yang Chen, Jian Ge, Min Ruan, Lin-Yang Zhu, Qing-Shu Zeng, Rui-Xiang Xia, He-Yu Ni
OBJECTIVE: To investigate the influence of divalent cation chelator EDTA and heparin sodium on the detection of ITP platelet-specific autoantibodies by the modified monoclonal antibody immobilization of platelet antigen assay (MAIPA) and to explore the relationship between types of platelet specific autoantibodies and glucocorticoid efficacy. METHODS: The samples were obtained from EDTA- and heparin- anticoagulant ITP patients, respectively, so as to detect the platelet-specific autoantibodies (GPIIb/IIIa and GPIbα) in 140 ITP samples by modified MAIPA, then the differences between these two methods were compared...
October 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
Tim Thijs, Katleen Broos, Stefaan J Soenen, Aline Vandenbulcke, Karen Vanhoorelbeke, Hans Deckmyn, Isabelle I Salles-Crawley
In recent years, candidate genes and proteins implicated in platelet function have been identified by various genomic approaches. To elucidate their exact role, we aimed to develop a method to apply miRNA interference in platelet progenitor cells by using GPIbα as a proof-of-concept target protein. After in silico and in vitro screening of siRNAs targeting GPIbα (siGPIBAs), we developed artificial miRNAs (miGPIBAs), which were tested in CHO cells stably expressing GPIb-IX complex and megakaryoblastic DAMI cells...
2015: PloS One
P A Basciano, J Matakas, A Pecci, E Civaschi, C Cagioni, N Bompiani, P Burger, P Christos, J P Snyder, J Bussel, C L Balduini, P Giannakakou, P Noris
BACKGROUND: Single nucleotide polymorphisms (SNPs) in platelet-associated genes partly explain inherent variability in platelet counts. Patients with monoallelic Bernard Soulier syndrome due to the Bolzano mutation (GPIBA A156V) have variable platelet counts despite a common mutation for unknown reasons. OBJECTIVES: We investigated the effect of the most common SNP (R307H) in the hematopoietic-specific tubulin isotype β-1 in these Bernard Soulier patients and potential microtubule-based mechanisms of worsened thrombocytopenia...
April 2015: Journal of Thrombosis and Haemostasis: JTH
Sri R Madabhushi, Changjie Zhang, Anju Kelkar, Kannayakanahalli M Dayananda, Sriram Neelamegham
BACKGROUND: Von Willebrand Factor (VWF) A1-domain binding to platelet receptor GpIbα is an important fluid-shear dependent interaction that regulates both soluble VWF binding to platelets, and platelet tethering onto immobilized VWF. We evaluated the roles of different structural elements at the N-terminus of the A1-domain in regulating shear dependent platelet binding. Specifically, the focus was on the VWF D'D3-domain, A1-domain N-terminal flanking peptide (NFP), and O-glycans on this peptide...
October 2014: Journal of the American Heart Association
Jana Ulehlova, Ludek Slavik, Jana Kucerova, Vera Krcova, Jan Vaclavik, Karel Indrak
METHODS: The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance...
September 2014: Genetic Testing and Molecular Biomarkers
Hassan Kassassir, Karolina Siewiera, Radosław Sychowski, Cezary Watała
BACKGROUND: The effects of blood platelet inhibitors are often not quite equivalent under in vivo and in vitro conditions. Amongst various models of human pathology using laboratory animals, mice offer several benefits that make them convenient tools for studying the putative therapeutic value of various compounds. However, despite its advantages, the mouse model has methodological limitations concerning the small amount of blood available and technical difficulties with its collection...
2013: Pharmacological Reports: PR
Shahnaz Ali, Kanjaksha Ghosh, Shrimati Shetty
Bernard-Soulier syndrome (BSS) is a severe inherited bleeding disorder due to defects in GPIb/IX/V, a platelet receptor that normally functions as a platelet membrane receptor for von Willebrand factor, thrombin and factor XI. BSS results from mutations in GP1BA, GP1BB or GP9 genes. In 15 patients with Bernard-Soulier syndrome from Western India, we amplified the entire coding sequences of GP1BA, GP1BB and GP9 genes and directly sequenced them. Twelve homozygous changes have been identified, out of which ten were novel mutations...
March 2014: Annals of Hematology
Sayer I Al-Azzam, Karem H Alzoubi, Omar F Khabour, Deniz Tawalbeh, Ola Al-Azzeh
OBJECTIVE: Aspirin is an antiplatelet agent commonly used in treatment of patients with high risk to develop stroke and myocardial infarction. However, inter-individual variability regarding the inhibition of platelet function by aspirin is well documented. In this study, the correlation between platelet glycoproteins (GPIa C807T and GPIba C-5T) and cyclooxygenase 2 (COX-2G-765C) polymorphisms and antiplatelet response in patients treated with aspirin was investigated. METHODS: Jordanian adult patients (n=584) who are taking aspirin as an antiplatelet agent participated in the study...
September 10, 2013: Gene
M A Avdonina, T V Nasedkina, A Iu Ikonnikova, E V Bondarenko, P A Slominskiĭ, N A Shamalov, I M Shetova, S A Limborskaia, A S Zasedatelev, V I Skvortsova
Allele and genotype frequencies of 10 single nucleotide polymorphisms in F12, PON1, PON2, NOS2, PDE4D, HIF1a,GPIba, CYP11B2 genes were studied in a group of Russian patients with ischemic stroke (IS) from central regions of the Russian Federation and healthy donors matched for sex, age and ethnicity. The genotyping procedure included the amplification of selected DNA sequences with the following hybridization of fluorescently-labeled regions with allele-specific DNA-probes immobilized on a biochip. An analysis of allele and genotype frequencies for each gene in IS patients and controls did not reveal any significant differences...
2012: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Patrizia Noris, Silverio Perrotta, Roberta Bottega, Alessandro Pecci, Federica Melazzini, Elisa Civaschi, Sabina Russo, Silvana Magrin, Giuseppe Loffredo, Veronica Di Salvo, Giovanna Russo, Maddalena Casale, Daniela De Rocco, Claudio Grignani, Marco Cattaneo, Carlo Baronci, Alfredo Dragani, Veronica Albano, Momcilo Jankovic, Saverio Scianguetta, Anna Savoia, Carlo L Balduini
BACKGROUND: Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients. DESIGN AND METHODS: Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of an autosomal, dominant form of thrombocytopenia of unknown origin...
January 2012: Haematologica
E Sumitha, G R Jayandharan, S David, R R Jacob, G Sankari Devi, B Bargavi, S Shenbagapriya, S C Nair, A Abraham, B George, A Viswabandya, V Mathews, M Chandy, A Srivastava
BACKGROUND: Bernard-Soulier syndrome (BSS) is an extremely rare (1:1 million) bleeding disorder of platelet adhesion, caused by defects in the glycoprotein (GP)Ib/IX/V complex. PATIENTS AND METHODS: The diagnosis in 27 patients was based on low platelet count, presence of giant platelets and aggregometry studies. Flow cytometry to assess the surface GPIb/IX/V complex showed reduced (7.7-57%) expression. gDNA was screened for mutations in the GPIBA, GPIBB, GP9 genes using PCR-conformation sensitive gel electrophoresis (CSGE)...
August 2011: Journal of Thrombosis and Haemostasis: JTH
Jane E Freedman, Martin G Larson, Kahraman Tanriverdi, Christopher J O'Donnell, Kristine Morin, Amanda S Hakanson, Ramachandran S Vasan, Andrew D Johnson, Mark D Iafrati, Emelia J Benjamin
BACKGROUND: Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in the abundance of transcripts has been demonstrated in malignancies, but gene expression from a large community-based cohort examining risk of cardiovascular disease has never been reported. METHODS AND RESULTS: On the basis of preliminary microarray data and previously suggested genes from the literature, we measured expression of 48 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from RNA derived from isolated platelets and leukocytes...
July 13, 2010: Circulation
Matthew Auton, Katie E Sowa, Scott M Smith, Erik Sedlák, K Vinod Vijayan, Miguel A Cruz
This study used recombinant A1A2A3 tri-domain proteins to demonstrate that A domain association in von Willebrand factor (VWF) regulates the binding to platelet glycoprotein Ibalpha (GPIbalpha). We performed comparative studies between wild type (WT) A1 domain and the R1450E variant that dissociates the tri-domain complex by destabilizing the A1 domain. Using urea denaturation and differential scanning calorimetry, we demonstrated the destabilization of the A1 domain structure concomitantly results in a reduced interaction among the three A domains...
July 23, 2010: Journal of Biological Chemistry
Constantino Martínez, Ana Isabel Antón, Javier Corral, Teresa Quiroga, Olga Panes, María Luisa Lozano, Rocío González-Conejero, Raúl Teruel, Leyre Navarro-Núñez, Jaime Pereira, Diego Mezzano, Vicente Vicente, José Rivera
Polymorphisms affecting platelet receptors and intracellular proteins have been extensively studied in relation to their potential influence in thrombosis and haemorrhages. However, few reports have addressed their impact on platelet function, with contradictory results. Limitations of these studies include, among others, small number of patients, the platelet functional parameters analyzed and their known variability in the healthy population. We studied the effect of six polymorphisms [ITGB3 1565T > C (HPA-1), GPIBA variable number tandem repeat and 524C > T (HPA-2), ITGA2 807C > T, ADRA2A 1780A > G, and TUBB1 Q43P] on platelet function in 286 healthy subjects and their potential pathogenetic role in 160 patients with hereditary mucocutaneous bleeding of unknown cause...
June 2009: British Journal of Haematology
Thomas J Kunicki, Shirley A Williams, Diane J Nugent, Paul Harrison, Helen C Segal, Anila Syed, Peter M Rothwell
We studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins alpha2beta1and alphaIIbbeta3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibalpha and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1)...
January 2009: Thrombosis and Haemostasis
Alexandre C Zago, Daniel I Simon, Yunmei Wang, Masashi Sakuma, Zhiping Chen, Kevin Croce, Valentin Ustinov, Can Shi, Eulógio E Martinez Filho
OBJECTIVE: To assess the importance of the interaction between leukocyte integrin Mac-1 (a Mb 2) and platelet glycoprotein (GP) Ib-a for leukocyte recruitment after vascular injury and the effect of the neutralization of the Mac-1-GPIba interaction on cell proliferation and the neointimal hyperplasia triggered by the vascular injury. METHODS: A peptide called M2 or anti-M2 antibody was developed to block the Mac-1-GPIba interaction. This peptide was injected and compared to a control-peptide in C57B1/6J mice submitted to vascular injury of the femoral artery with a guide wire...
January 2008: Arquivos Brasileiros de Cardiologia
Paquita Nurden, François Lanza, Cécile Bonnafous-Faurie, Alan Nurden
No abstract text is available yet for this article.
February 2007: Thrombosis and Haemostasis
Luca Pontiggia, Beat Steiner, Hans Ulrichts, Hans Deckmyn, Marc Forestier, Jürg H Beer
We studied the inhibition of platelet microparticle (MP) formation and thrombin generation under high shear forces. We hypothesized that an inhibitor of the GPIb a -von Willebrand factor (vWF) interaction would be more effective in suppressing MP formation and thrombin generation than GPIIb/IIIa inhibitors. Platelet-rich plasma (PRP) anticoagulated with PPACK (D-Phe-Pro-Arg chloromethyl ketone) was exposed in a cone-and-plate viscometer (shear: 5,000 s(-1) for 5 min) in the presence of antagonists to GPIb a (the monoclonal antibody [Mab] Ib-23) or to GPIIb/IIIa (abciximab, tirofiban, eptifibatide) at their IC90 determined in platelet aggregometry with ristocetin or ADP, respectively...
December 2006: Thrombosis and Haemostasis
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