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upregulation of P2Y12 in platelet

Yongjian Yue, Shengguo Liu, Xuemei Han, Minlian Wang, Yazhen Li, Qijun Huang, Bo Li, Mo Yang, Yong Dai, Yingyun Fu
The disorders of hemostasis and coagulation were believed to be the main contributors to the pathogenesis of pulmonary thromboembolism (PTE), and platelets are the basic factors regulating hemostasis and coagulation and play important roles in the process of thrombosis. This study investigated the proteome of human umbilical vein endothelial cells (HUVECs) with platelet endothelial aggregation receptor-1 (PEAR1) knockdown using the isobaric tags for relative and absolute quantitation (iTRAQ) method and analyzed the role of differential abundance proteins (DAPs) in the regulation of platelets aggregation...
February 27, 2019: Journal of Cellular Biochemistry
Ming Zhou, Meng Gao, Yanwei Luo, Rong Gui, Hongwen Ji
Platelet hyperaggregation and hypercoagulation are associated with increase of thrombogenic risk, especially in patients with type 2 diabetes (T2D). High activity of P2Y12 receptor is found in T2D patients, exposing such patients to a prothrombotic condition. P2Y12 is a promising target for antiplatelet, but due to P2Y12 receptor constitutive activation, the clinical practical phenomena such as "clopidogrel resistance" are commonly occurring. In this study, we investigate the role of lncRNA on platelet activation...
April 4, 2018: Platelets
Omar Elaskalani, Marco Falasca, Niamh Moran, Michael C Berndt, Pat Metharom
Platelets have been demonstrated to be vital in cancer epithelial-mesenchymal transition (EMT), an important step in metastasis. Markers of EMT are associated with chemotherapy resistance. However, the association between the development of chemoresistance, EMT, and the contribution of platelets to the process, is still unclear. Here we report that platelets regulate the expression of (1) human equilibrative nucleoside transporter 1 (hENT1) and (2) cytidine deaminase (CDD), markers of gemcitabine resistance in pancreatic cancer...
October 24, 2017: Cancers
Paloma Guillem-Llobat, Melania Dovizio, Annalisa Bruno, Emanuela Ricciotti, Valerio Cufino, Angela Sacco, Rosalia Grande, Sara Alberti, Vincenzo Arena, Mariangela Cirillo, Carlo Patrono, Garret A FitzGerald, Dieter Steinhilber, Alessandro Sgambato, Paola Patrignani
We investigated whether platelets prime colon cancer cells for metastasis and whether pharmacological inhibition of platelet function may prevent it. Coculturing HT29 human colon carcinoma cells with human platelets led to the induction of mesenchymal-like cancer cells characterized by downregulation of E-cadherin and upregulation of Twist1, enhanced cell mobility and a proaggregatory action on platelets. These changes were prevented by different antiplatelet agents, aspirin[an inhibitor of cyclooxygenase(COX)-1], DG-041[an antagonist of prostaglandin(PG)E2 EP3 receptor] and ticagrelor (a P2Y12 receptor antagonist)...
May 31, 2016: Oncotarget
Shuisheng Yang, Jingfeng Zhao, Yuxiang Chen, Minxiang Lei
Diabetes is an established risk factor for ischemic stroke, but the associated molecular mechanisms remain to be fully elucidated. This study investigated the role of plasma and platelet microRNAs and their targeting proteins in the activation of platelets and their association with the occurrence of ischemic stroke in patients with type 2 diabetes mellitus (T2DM). Results showed that the expressions of platelet and plasma miR-144 and miR-223 were significantly altered in T2DM patients with or without ischemic stroke compared to that in healthy controls, but these changes were more significant in T2DM patients with ischemic stroke...
July 2016: Cardiovascular Toxicology
Mercy Halleluyah Periayah, Ahmad Sukari Halim, Nik Soriani Yaacob, Arman Zaharil Mat Saad, Abdul Rahim Hussein, Ahmad Hazri Abdul Rashid, Zanariah Ujang
Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0...
2014: BioMed Research International
Manjyot K Nanhwan, Shukuan Ling, Monica Kodakandla, Sven Nylander, Yumei Ye, Yochai Birnbaum
OBJECTIVE: In a phase III clinical trial (PLATelet inhibition and patient Outcomes, PLATO), ticagrelor provided better clinical outcomes than clopidogrel in patients with acute coronary syndromes. In addition to P2Y12-receptor antagonism, ticagrelor prevents cell uptake of adenosine and has proven able to augment adenosine effects. Adenosine protects the heart against ischemia-reperfusion injury. We compared the effects of clopidogrel and ticagrelor on myocardial infarct size (IS). APPROACH AND RESULTS: Rats received oral ticagrelor (0, 75, 150, or 300 mg/kg/d) or clopidogrel (30 or 90 mg/kg/d) for 7 days and underwent 30-minute coronary artery ligation and 24-hour reperfusion...
September 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Gergely Horváth, Flóra Gölöncsér, Cecilia Csölle, Kornél Király, Rómeó D Andó, Mária Baranyi, Bence Koványi, Zoltán Máté, Kristina Hoffmann, Irina Algaier, Younis Baqi, Christa E Müller, Ivar Von Kügelgen, Beáta Sperlágh
In this study the role of P2Y12 receptors (P2Y12R) was explored in rodent models of inflammatory and neuropathic pain and in acute thermal nociception. In correlation with their activity to block the recombinant human P2Y12R, the majority of P2Y12R antagonists alleviated mechanical hyperalgesia dose-dependently, following intraplantar CFA injection, and after partial ligation of the sciatic nerve in rats. They also caused an increase in thermal nociceptive threshold in the hot plate test. Among the six P2Y12R antagonists evaluated in the pain studies, the selective P2Y12 receptor antagonist PSB-0739 was most potent upon intrathecal application...
October 2014: Neurobiology of Disease
Siva Suryadevara, Masafumi Ueno, Antonio Tello-Montoliu, Jose Luis Ferreiro, Bhaloo Desai, Fabiana Rollini, Lyndon C Box, Martin Zenni, Luis A Guzman, Theodore A Bass, Dominick J Angiolillo
Patients with type 2 diabetes mellitus (T2DM) have impaired clopidogrel-induced antiplatelet effects, which may be in part attributed to their reduced sensitivity to insulin and consequently, results in upregulation of the P2Y12 signalling pathway. It has been hypothesised that insulin sensitising strategies may enhance clopidogrel-mediated P2Y12 inhibitory effects. The aim of this pilot pharmacodynamics (PD) study was to assess the impact of pioglitazone on clopidogrel-mediated P2Y12 inhibitory effects in patients with T2DM...
November 2012: Thrombosis and Haemostasis
Karl Egan, Darragh Crowley, Paul Smyth, Sharon O'Toole, Cathy Spillane, Cara Martin, Michael Gallagher, Aoife Canney, Lucy Norris, Niamh Conlon, Lynda McEvoy, Brendan Ffrench, Britta Stordal, Helen Keegan, Stephen Finn, Victoria McEneaney, Alex Laios, Jens Ducrée, Eimear Dunne, Leila Smith, Michael Berndt, Orla Sheils, Dermot Kenny, John O'Leary
Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line...
2011: PloS One
Olivier Morel, Laurence Kessler, Patrick Ohlmann, Pierre Bareiss
Atherothrombosis--defined as atherosclerotic lesion disruption with superimposed thrombus formation--is a leading cause of death in patients with diabetes mellitus. Platelets play a pivotal role in atherothrombosis and platelets of diabetic patients are hyperreactive. Numerous studies have investigated the usefulness of antiplatelet therapy for primary and secondary prevention of atherothrombotic events in diabetic patients. However, there are limited evidences that aspirin may be effective in the reduction of atherothrombotic complication in this population...
October 2010: Atherosclerosis
Gouri Shanker, Jimmy L Kontos, Delrae M Eckman, Deborah Wesley-Farrington, David C Sane
BACKGROUND: P2Y12 is the major platelet receptor that mediates ADP-induced aggregation. P2Y12 is also expressed by vascular cells. The factors that regulate P2Y12 expression have not been determined. Since nicotine (NIC) has effects on platelet activation and vascular function, and because nicotinic and purinerigic receptors may interact, we determined whether nicotine altered P2Y12 expression. METHODS: Four cell lines (human coronary artery endothelial cells, HCAEC; human umbilical vein endothelial cells, HUVEC; human aortic smooth muscle cells, HASMC; and human megakaryoblastic cells, MEG-01) were cultured in the absence or presence of nicotine...
December 2006: Journal of Thrombosis and Thrombolysis
Dominick J Angiolillo, Esther Bernardo, Celia Ramírez, Marco A Costa, Manel Sabaté, Pilar Jimenez-Quevedo, Rosana Hernández, Raul Moreno, Javier Escaned, Fernando Alfonso, Camino Bañuelos, Theodore A Bass, Carlos Macaya, Antonio Fernandez-Ortiz
OBJECTIVES: This study sought to assess the influence of type 2 diabetes mellitus (T2DM) and the impact of hypoglycemic treatment (insulin vs. noninsulin) on platelet function profiles in patients treated with dual oral antiplatelet therapy. BACKGROUND: Insulin inhibits platelet aggregation by suppressing the P2Y12 pathway. However, T2DM patients have a loss of responsiveness to insulin that leads to upregulation of the P2Y12 pathway, increased platelet reactivity, and reduced responsiveness to antiplatelet agents...
July 18, 2006: Journal of the American College of Cardiology
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