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P2Y 12

Brian R Branchford, Timothy J Stalker, Luke Law, Gilbert Acevedo, Susan Sather, Christine Brzezinski, Katina M Wilson, Katherine Minson, Alisa B Lee-Sherick, Pavel Davizon-Castillo, Christopher Ng, Weihe Zhang, Keith B Neeves, Steven R Lentz, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Deborah DeRyckere, Lawrence F Brass, Douglas K Graham, Jorge A Di Paola
BACKGROUND: Gas6 signals through the TAM (TYRO-3, AXL, MERTK) receptor family mediating platelet activation and thrombus formation via activation of the aggregate-stabilizing αIIb β3 integrin. OBJECTIVE: Here we describe anti-thrombotic effects mediated by UNC2025, a small molecule MERTK tyrosine kinase inhibitor. METHODS: MERTK phosphorylation and downstream signaling were assessed by immunoblot. Light transmission aggregometry, flow cytometry, and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregate formation in vitro...
October 17, 2017: Journal of Thrombosis and Haemostasis: JTH
Kuan Ken Lee, Nicky Welton, Anoop S Shah, Philip D Adamson, Sofia Dias, Atul Anand, David E Newby, Nicholas L Mills, David A McAllister
OBJECTIVE: To estimate the absolute treatment effects of newer P2Y12 inhibitors (ticagrelor and prasugrel) compared with clopidogrel in men and women with acute coronary syndrome (ACS). METHODS: We searched Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials of oral P2Y12 inhibitors for acute stroke or ACS. Age-specific and sex-specific mortality was obtained for all patients admitted to hospital with myocardial infarction in Scotland from 2006 to 2010 (prior to introduction of prasugrel or ticagrelor)...
October 5, 2017: Heart: Official Journal of the British Cardiac Society
Phillip A Choi, Phillip V Parry, Joshua S Bauer, Benjamin E Zusman, David M Panczykowski, Ava M Puccio, David O Okonkwo
BACKGROUND: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y 12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y 12 inhibitors in the cardiac population. OBJECTIVE: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury. METHODS: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy...
January 1, 2017: Neurosurgery
J Todd Belcik, Brian P Davidson, Aris Xie, Melinda D Wu, Mrinal Yadava, Yue Qi, Sherry Liang, Chae Ryung Chon, Azzdine Y Ammi, Joshua Field, Leanne Harmann, William M Chilian, Joel Linden, Jonathan R Lindner
BACKGROUND: Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. METHODS: Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1...
March 28, 2017: Circulation
Marta Kuczeriszka, Leszek Dobrowolski, Agnieszka Walkowska, Janusz Sadowski
BACKGROUND: Purine P2X and P2Y receptors (P2-R) are involved in control of renal circulation, especially in the medulla, wherein they appear to interact with angiotensin II (Ang II). Our experimental approach enabled examination of interaction with Ang II per se, in the absence of blood pressure elevation. In this whole-kidney functional study we focused on the influence of P2X1-R on perfusion of the renal medulla. METHODS: Acute experiments were conducted with normal rats, untreated or subjected to two weeks' infusion of Ang II (osmotic minipumps)...
December 2016: Pharmacological Reports: PR
Wen-Mei Zhang, Yan Liu, Tao-Tao Li, Chun-Mei Piao, Ou Liu, Jun-Ling Liu, Yong-Fen Qi, Li-Xin Jia, Jie Du
Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. However, the mechanism whereby signaling leads to SMC loss is unclear. We used senescence-associated (SA)-β-gal staining and analysis of expression of senescence-related proteins (p53, p21, p19) to show that excessive mechanical stretch (20% elongation, 3600cycles/h, 48h) induced SMC senescence. SMC senescence was also detected in TAAD specimens from both mice and humans...
October 2016: Journal of Molecular and Cellular Cardiology
Chang-Chieh Wu, Fu-Ming Tsai, Mao-Liang Chen, Semon Wu, Ming-Cheng Lee, Tzung-Chieh Tsai, Lu-Kai Wang, Chun-Hua Wang
Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs...
2016: BioMed Research International
Kasumi Moriguchi-Mori, Hironori Higashio, Kanako Isobe, Miho Kumagai, Kana Sasaki, Yoh-ichi Satoh, Akiyoshi Kuji, Tomoyuki Saino
Adenosine 5'-triphosphate (ATP) can act as an extracellular signal that regulates various cellular functions. The present study aimed to determine which purinoceptors play a role in ATP-induced changes in intracellular Ca(2+) ([Ca(2+)]i) and amylase secretion in mouse parotid glands. ATP induced a steep increase in [Ca(2+)]i in acinar cells. The removal of extracellular Ca(2+) or the use of Ca(2+) channel blockers slightly inhibited this increase. Inhibition of PLCγ by U73122 and of IP3 by xestospongin C did not completely block this increase...
2016: Biomedical Research
T Horváth, G Polony, Á Fekete, M Aller, G Halmos, B Lendvai, A Heinrich, B Sperlágh, E S Vizi, T Zelles
Hearing and its protection is regulated by ATP-evoked Ca(2+) signaling in the supporting cells of the organ of Corti, however, the unique anatomy of the cochlea hampers observing these mechanisms. For the first time, we have performed functional ratiometric Ca(2+) imaging (fura-2) in three different supporting cell types in the hemicochlea preparation of hearing mice to measure purinergic receptor-mediated Ca(2+) signaling in pillar, Deiters' and Hensen's cells. Their resting [Ca(2+)]i was determined and compared in the same type of preparation...
February 2016: Neurochemical Research
U Banderali, E Brochiero, S Lindenthal, C Raschi, S Bogliolo, J Ehrenfeld
1 The effect of extracellular nucleotides applied on the apical side of polarised A6 cells grown on permeant filters was investigated by measuring the changes in (i) the (36) Cl efflux through the apical membranes, (ii) the intracellular chloride concentrations (aCli , measured with N-(6-methoxyquinolyl) acetoethyl ester, MQAE), (iii) ICl , the short-circuit current in the absence of Na(+) transport and (iv) the characteristics of the apical chloride channels using a patch-clamp approach. 2 ATP or UTP (0.1-500 μm) transiently stimulated ICl ...
September 1999: Journal of Physiology
Peter Clemmensen, Matthew T Roe, Judith S Hochman, Derek D Cyr, Megan L Neely, Darren K McGuire, Jan H Cornel, Kurt Huber, Dmitry Zamoryakhin, Harvey D White, Paul W Armstrong, Keith A A Fox, Dorairaj Prabhakaran, Erik Magnus Ohman
BACKGROUND: Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. METHODS: Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 [39%]) and men (n = 5,676 [61%]) randomized to prasugrel 10 mg/d (5 mg/d for patients ≥75 years and/or <60 kg) versus clopidogrel 75 mg/d...
October 2015: American Heart Journal
Gilles Montalescot, David Brieger, Anthony J Dalby, Seung-Jung Park, Roxana Mehran
The duration of dual antiplatelet therapy (DAPT) after coronary stenting has been evaluated in randomized studies with apparently conflicting results. Although longer exposure associates with more bleeding complications, late stent thrombosis (ST) and myocardial infarction are reduced. In addition, as new drug-eluting stents carry a lower risk of ST compared with the first-generation drug-eluting stents and possibly even bare-metal stents, a shift toward better protection from ST may have an effect on the duration and intensity of DAPT...
August 18, 2015: Journal of the American College of Cardiology
Connie N Hess, Stefan James, Renato D Lopes, Daniel M Wojdyla, Megan L Neely, Danny Liaw, Emil Hagstrom, Deepak L Bhatt, Steen Husted, Shaun G Goodman, Basil S Lewis, Freek W A Verheugt, Raffaele De Caterina, Hisao Ogawa, Lars Wallentin, John H Alexander
BACKGROUND: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES: We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. METHODS: This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate...
August 18, 2015: Journal of the American College of Cardiology
Sophia L B Oliveira, Cleber A Trujillo, Priscilla D Negraes, Henning Ulrich
Purinergic receptors belong to the most ancient neurotransmitter system. While their relevance in neurotransmission is well characterized, it has become clear that they have many other cellular functions. During development, they participate in regulation of proliferation and differentiation of stem cells. Here, we used rat embryonic telencephalon neurosphere cultures to detect purinergic P2 receptor subtype expression and possible synergistic actions of these receptors with NGF. Neurospheres proliferate in the presence of EGF and FGF-2; however, upon depletion of these growth factors, they migrate and differentiate into neurons and glial phenotypes...
September 2015: Neurochemical Research
Shahzeb, Nasir Ali, Abdul Hadi, Ibrahim Shah, Adnan Mehmood Gul, Jabar Ali, Mohammad Hafizullah
BACKGROUND: Percutaneous coronary interventions are almost always preceded by the loading dose of platelets inhibiter drugs such as clopidogrel or prasugrel and followed by maintenance therapy to decrease the mortality and morbidity due to stent thrombosis. This study was conducted to compare the efficacy of clopidogrel and prasugrel for inhibiting platelet aggregation among patients undergoing elective percutaneous coronary intervention. METHODS: This randomized controlled trial study was done in Department of Cardiology, Postgraduate Medical Institute Govt...
January 2015: Journal of Ayub Medical College, Abbottabad: JAMC
Robin Mathews, Tracy Y Wang, Emily Honeycutt, Timothy D Henry, Marjorie Zettler, Michael Chang, Gregg C Fonarow, Eric D Peterson
BACKGROUND: Persistent use of secondary prevention therapies after acute myocardial infarction (MI) is critical to optimizing long-term outcomes. METHODS: Medication persistence was assessed among 7,955 MI patients in 216 hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome study from 2010 to 2012. Persistence was defined as continuation of aspirin, adenosine diphosphate receptor inhibitors, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins from discharge to 6 months post-MI...
July 2015: American Heart Journal
Petr Widimsky, Zuzana Motovska, Leonardo Bolognese, Dariusz Dudek, Christian Hamm, Jean-Francois Tanguay, Jurrien Ten Berg, Eileen Brown, LeRoy LeNarz, Debra L Miller, Gilles Montalescot
BACKGROUND: When considering antiplatelet therapy for acute coronary syndrome (ACS), it is essential to balance benefits (less thrombotic/ischaemic events) versus bleeding risks related to intense platelet inhibition via antagonism of P2Y12 receptors. This analysis aimed to identify predictors of bleeding events among A Comparison of Prasugrel at the Time of PCI or as Pretreatment at the Time of Diagnosis in Patients with NSTEACS (ACCOAST) study population. METHODS AND RESULTS: The ACCOAST study randomised 4033 patients with non-ST-segment elevation myocardial infarction (NSTEMI) to (A) a 30 mg prasugrel loading dose (LD) followed by coronary angiography with an additional 30 mg prasugrel at the time of percutaneous coronary intervention (PCI) or (B) a placebo LD followed by a 60 mg prasugrel at the time of PCI...
August 2015: Heart: Official Journal of the British Cardiac Society
Yumei Ye, Gilad D Birnbaum, Jose R Perez-Polo, Manjyot K Nanhwan, Sven Nylander, Yochai Birnbaum
OBJECTIVE: In addition to P2Y12 receptor antagonism, ticagrelor inhibits adenosine cell uptake. Prior data show that 7-day pretreatment with ticagrelor limits infarct size. We explored the acute effects of ticagrelor and clopidogrel on infarct size and potential long-term effects on heart function. APPROACH AND RESULTS: Rats underwent 30-minute ischemia per 24-hour reperfusion. (1) Ticagrelor (10 or 30 mg/kg) or clopidogrel (12.5 mg/kg) was given via intraperitoneal injection 5 minutes before reperfusion...
August 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Jonathon M Willets, Craig A Nash, Richard D Rainbow, Carl P Nelson, R A John Challiss
Prolonged vasoconstrictor-stimulated phospholipase C activity can induce arterial constriction, hypertension, and smooth muscle hypertrophy/hyperplasia. Arrestin proteins are recruited by agonist-occupied G protein-coupled receptors to terminate signaling and counteract changes in vascular tone. Here we determine whether the development of hypertension affects arrestin expression in resistance arteries and how such changes alter arterial contractile signaling and function. Arrestin2/3 expression was increased in mesenteric arteries of 12-wk-old spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) controls, while no differences in arrestin expression were observed between 6-wk-old SHR and WKY animals...
August 1, 2015: American Journal of Physiology. Cell Physiology
Shi-tang Ma, Guo-liang Dai, Xiao-gui Cheng, Wen-zhu Zhao, Bing-ting Sun, Wen-zheng Ju, Heng-shan Tan
OBJECTIVE: To study the synergistic action of Compound Danshen Dripping Pill (CDDP) on Clopidogrel Bisulfate (CPG) counteracting platelet aggregation. METHODS: 40 Sprague-Dawley (SD) rats were randomized into four groups: normal control group (CMC-Na), CPG alone group (30 mg/kg), CDDP alone group (324 mg/kg), co-administration group (CPG 30 mg/kg and CDDP 324 mg/kg). The rats received gastric infusion of corresponding drugs for 21 continuous days. Blood sample of SD rats were collected by puncture of the abdominal artery for the determination of coagulation parameters such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) concentration and thrombin time (TT) in each group...
October 2014: Zhong Yao Cai, Zhongyaocai, Journal of Chinese Medicinal Materials
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