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Caroline Kardeby, Knut Fälker, Elizabeth J Haining, Maarten Criel, Madelene Lindkvist, Ruben Barroso, Peter Påhlsson, Liza U Ljungberg, Mattias Tengdelius, G Ed Rainger, Stephanie Watson, Johannes A Eble, Marc F Hoylaerts, Jonas Emsley, Peter Konradsson, Steve P Watson, Yi Sun, Magnus Grenegård
Fucoidans are sulfated fucose-based polysaccharides that activate platelets and have pro- and anticoagulant effects; thus, they may have therapeutic value. In the present study, we show that 2 synthetic sulfated α-l-fucoside-pendant glycopolymers (with average monomeric units of 13 and 329) and natural fucoidans activate human platelets through a Src- and phosphatidylinositol 3-kinase (PI3K)-dependent and Syk-independent signaling cascade downstream of the platelet endothelial aggregation receptor 1 (PEAR1)...
February 12, 2019: Blood Advances
Shunsuke Miyashima, Pawel Roszak, Iris Sevilem, Koichi Toyokura, Bernhard Blob, Jung-Ok Heo, Nathan Mellor, Hanna Help-Rinta-Rahko, Sofia Otero, Wouter Smet, Mark Boekschoten, Guido Hooiveld, Kayo Hashimoto, Ondřej Smetana, Riccardo Siligato, Eva-Sophie Wallner, Ari Pekka Mähönen, Yuki Kondo, Charles W Melnyk, Thomas Greb, Keiji Nakajima, Rosangela Sozzani, Anthony Bishopp, Bert De Rybel, Ykä Helariutta
Apical growth in plants initiates upon seed germination, whereas radial growth is primed only during early ontogenesis in procambium cells and activated later by the vascular cambium1 . Although it is not known how radial growth is organized and regulated in plants, this system resembles the developmental competence observed in some animal systems, in which pre-existing patterns of developmental potential are established early on2,3 . Here we show that in Arabidopsis the initiation of radial growth occurs around early protophloem-sieve-element cell files of the root procambial tissue...
January 9, 2019: Nature
Lei Pi, Yufen Xu, Lanyan Fu, Li Zhang, Yunfeng Liu, Huazhong Zhou, Di Che, Xiaoqiong Gu
Kawasaki disease (KD) is an acute systemic vasculitis that is most seriously complicated by coronary artery aneurysm (CAA). The polymorphisms of platelet endothelial aggregation receptor 1 (PEAR1), notably rs12041331 and rs12566888, were found to be closely related to cardiac disease. However, little is known regarding the connection between PEAR1 and KD. In this study, we genotyped PEAR1 rs12566888 and rs12041331 in 637 healthy infants and 694 KD patients (74 with CAA). Subsequently, odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the strength of their relationships...
January 2019: Annals of Human Genetics
Fabian Stimpfle, Maike Bauer, Dominik Rath, Elke Schaeffeler, Matthias Schwab, Meinrad Gawaz, Stefan Winter, Tobias Geisler
Introduction: Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in PEAR1 . Methods: In 582 consecutive patients with stable coronary artery disease (CAD) or acute coronary syndrome (ACS) scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel, or Ticagrelor, SNP analysis for rs12566888, rs2768759, rs41273215, rs3737224, and rs822442 was performed...
2018: Frontiers in Pharmacology
Juraj Sokol, Maria Skerenova, Jela Ivankova, Tomas Simurda, Jan Stasko
The aim of this study was to evaluate the genetic variability of the selected single nucleotide polymorphisms (SNPs) and examine the association between these SNPs and risk for deep vein thrombosis (DVT) in patients with sticky platelet syndrome (SPS). We examined 84 patients with SPS and history of DVT and 101 healthy individuals. We were interested in 2 SNPs within platelet endothelial aggregation receptor 1 (PEAR1) gene (rs12041331 and rs12566888), 2 SNPs within mkurine retrovirus integration site 1 gene (rs7940646 and rs1874445), 1 SNP within Janus kinase 2 gene (rs2230722), 1 SNP within FCER1G gene (rs3557), 1 SNP within pro-platelet basic protein (rs442155), 4 SNPs within alpha2A adrenergic receptor 2A (ADRA2A; rs1800545, rs4311994, rs11195419, and rs553668), and 1 SNP within sonic hedgehog gene (rs2363910)...
October 2018: Clinical and Applied Thrombosis/hemostasis
Benedetta Izzi, Fabrizia Noro, Katrien Cludts, Kathleen Freson, Marc F Hoylaerts
Chromosomal interactions connect distant enhancers and promoters on the same chromosome, activating or repressing gene expression. PEAR1 encodes the Platelet-Endothelial Aggregation Receptor 1, a contact receptor involved in platelet function and megakaryocyte and endothelial cell proliferation. PEAR1 expression during megakaryocyte differentiation is controlled by DNA methylation at its first CpG island. We identified a PEAR1 cell-specific methylation sensitive region in endothelial cells and megakaryocytes that showed strong chromosomal interactions with ISGL20L2 , RRNAD1 , MRLP24 , HDGF and PRCC , using available promoter capture Hi-C datasets...
April 3, 2018: International Journal of Molecular Sciences
Ya Feng Cui, Yun Qin Yan, Dan Liu, Yu Sheng Pang, Jiang Wu, Shu Feng Li, Hui Li Tong
C2C12 murine myoblasts are a common model for studying muscle differentiation. Platelet endothelial aggregation receptor-1 (PEAR1), an epidermal growth factor repeat-containing transmembrane receptor, is known to participate in platelet contact-induced activation. In the present study, we demonstrated that PEAR1 is involved in the differentiation of C2C12 murine myoblasts. Western blotting and immunofluorescence staining were used to determine PEAR1 expression and localization during C2C12 cell differentiation...
May 15, 2018: Experimental Cell Research
Ali R Keramati, Lisa R Yanek, Kruthika Iyer, Margaret A Taub, Ingo Ruczinski, Diane M Becker, Lewis C Becker, Nauder Faraday, Rasika A Mathias
Coronary artery disease (CAD) remains a major cause of mortality and morbidity worldwide. The aggregation of activated platelets on a ruptured atherosclerotic plaque is a critical step in most acute cardiovascular events like myocardial infarction. Platelet aggregation both at baseline and after aspirin is highly heritable. Genome-wide association studies (GWAS) have identified a common variant within the first intron of the platelet endothelial aggregation receptor1 (PEAR1), to be robustly associated with platelet aggregation...
March 19, 2018: Platelets
Xiao-Yan Nie, Jun-Lei Li, Si-Bei Qin, Yu Fu, Guang-Kai Liang, Lu-Wen Shi, Hong Shao, Jian Liu, Yun Lu
OBJECTIVE: To investigate the association between PEAR1 (platelet endothelial aggregation receptor-1) polymorphisms and cardiovascular outcomes in acute coronary syndrome (ACS) in patients treated with aspirin and clopidogrel. METHODS: We genotyped eight common PEAR1 SNPs (rs2768759, rs12566888, rs12041331, rs11264579, rs2644592, rs822441, rs822442, and rs4661012), also CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) in 196 Chinese patients with ACS. We assessed the association between PEAR1 polymorphisms and platelet inhibition rate (PIR) measured by thromboelastography (TEG)...
March 2018: Thrombosis Research
S Roullet, S Labrouche, C Carrie, H Auque, X Berard, G Freyburger
Essentials Acetylsalicylic acid (ASA) is prescribed to patients scheduled for carotid endarterectomy (CEA). We measured ASA efficacy during CEA by Multiplate® and searched for influencing factors. Most patients scheduled for CEA and treated by ASA are sensitive to this therapy. Influencing genomic factors are involved in ASA metabolism and in platelet function modulations. SUMMARY: Background Acetylsalicylic acid (ASA) is recommended before, during and after carotid endarterectomy (CEA)...
March 2018: Journal of Thrombosis and Haemostasis: JTH
Lukasz Milanowski, Fazila Rasul, Sylwia Natalia Gajda, Ceren Eyileten, Jolanta Siller-Matula, Marek Postula
BACKGROUND: Platelet hyperactivity has been implicated in 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...
2018: Current Pharmaceutical Design
Yi Yao, Xiao-Fang Tang, Chen He, Ying Song, Jing-Jing Xu, Xian-Min Meng, Bo Xu, Run-Lin Gao, Jin-Qing Yuan
AIMS: Platelet endothelial aggregation receptor-1 (PEAR1) is a platelet transmembrane protein that plays an important role on platelet aggregation. The aim of this study was to investigate whether PEAR1 genetic variations are associated with 1-year outcomes in Chinese patients with acute myocardial infarction after percutaneous coronary intervention. METHODS: A total of 647 consecutive Chinese patients with acute myocardial infarction that underwent percutaneous coronary intervention and that were exposed to standard dual antiplatelet therapy with aspirin and clopidogrel were enrolled in this study...
May 1, 2018: Journal of Atherosclerosis and Thrombosis
Qian Xiang, Shuang Zhou, Joshua P Lewis, Alan R Shuldiner, Guanhua Ren, Yimin Cui
BACKGROUND: Platelet endothelial aggregation receptor 1 (PEAR1) may affect platelet-platelet contact and aggregation. The aim of this study was to assess the association between PEAR1 polymorphisms and risks of platelet aggregation. METHODS: We searched the PubMed, EmBase, and Cochrane Library electronic databases for articles published through November 30th. 2016. Meta-analysis was performed to examine the relationship between PEAR1 and platelet aggregation and sensitivity analysis by removing individual study from meta-analysis...
2017: Current Pharmaceutical Design
Elliot Berinstein, Andrew Levy
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
Wen-Yi Yang, Thibault Petit, Nicholas Cauwenberghs, Zhen-Yu Zhang, Chang-Sheng Sheng, Lutgarde Thijs, Erika Salvi, Benedetta Izzi, Christophe Vandenbriele, Fang-Fei Wei, Yu-Mei Gu, Lotte Jacobs, Lorena Citterio, Simona Delli Carpini, Cristina Barlassina, Daniele Cusi, Marc F Hoylaerts, Peter Verhamme, Tatiana Kuznetsova, Jan A Staessen
BACKGROUND: Platelet Endothelial Aggregation Receptor 1 (PEAR1), a membrane protein highly expressed in platelets and endothelial cells, plays a role in platelet contact-induced activation, sustained platelet aggregation and endothelial function. Previous reports implicate PEAR1 rs12041331 as a variant influencing risk in patients with coronary heart disease. We investigated whether genetic variation in PEAR1 predicts cardiovascular outcome in a white population. METHODS: In 1938 participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes (51...
April 27, 2017: BMC Medical Genetics
J D Backman, L M Yerges-Armstrong, R B Horenstein, S Newcomer, S Shaub, M Morrisey, P Donnelly, M Drolet, K Tanner, M A Pavlovich, J R O'Connell, B D Mitchell, J P Lewis
Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)-induced platelet aggregation compared with noncarriers (P = 0...
March 2017: Clinical and Translational Science
Yingyun Fu, Silong Sun, Jie Liang, Shengguo Liu, Yiqi Jiang, Lan Xu, Junpu Mei
To explore the correlation between platelet endothelial aggregation receptor-1 (PEAR1) genetic polymorphism and pulmonary thromboembolism (PTE).Variant loci of the PEAR1 gene were screened in a PTE pedigree, followed by verification using Sanger sequencing. These polymorphic loci were validated in 101 PTE patients and 132 matched normal patients using MassARRAY single nucleotide polymorphism (SNP) genotyping methods. The frequency differences between the allele and genotypes were compared using the Hardy-Weinberg equilibrium test and Chi-square test...
December 2016: Medicine (Baltimore)
Mupeng Li, Yaodong Hu, Zhipeng Wen, Huilan Li, Xiaolei Hu, Yanjiao Zhang, Zanling Zhang, Jian Xiao, Jie Tang, Xiaoping Chen
1. Genetic polymorphisms in platelet endothelial aggregation receptor 1 (PEAR1) were associated with responsiveness to aspirin and P2Y12 receptor antagonists. This study aimed to investigate whether PEAR1 polymorphism is associated with ticagrelor pharmacodynamics in healthy Chinese subjects. 2. The in vitro inhibition of platelet aggregation (IPA) was evaluated before and after ticagrelor incubated with platelet-rich plasma from 196 healthy Chinese male subjects. Eight polymorphisms at PEAR1 locus were genotyped...
December 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Ling-Ling Peng, Yuan-Qi Zhao, Zi-Yi Zhou, Jing Jin, Min Zhao, Xin-Meng Chen, Ling-Yan Chen, Ye-Feng Cai, Jia-Li Li, Min Huang
AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine...
November 2016: Acta Pharmacologica Sinica
Maarten Criel, Benedetta Izzi, Christophe Vandenbriele, Laurens Liesenborghs, Soetkin Van Kerckhoven, Marleen Lox, Katrien Cludts, Elizabeth A V Jones, Thomas Vanassche, Peter Verhamme, Marc Hoylaerts
BACKGROUND: Platelet Endothelial Aggregation Receptor-1 (PEAR1) is a transmembrane platelet receptor that amplifies the activation of the platelet fibrinogen receptor (αIIbβ3) during platelet aggregation. In man, Pear1 polymorphisms are associated with changes in platelet aggregability. In this report, we characterized Pear1 expression and function in murine platelets. METHODS: Pear1 phosphorylation and signaling, platelet aggregation, α-degranulation and clot retraction were studied in WT and Pear1(-/-) platelets...
October 2016: Thrombosis Research
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