Publications
99 results found
Smyth E, Nelson M, Emerson M, 2015, Comparative impacts of antiretroviral HIV therapies on platelet function, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 13, Pages: 651-652, ISSN: 1538-7933
Emerson M, Ilkan Z, Mustafa F, et al., 2015, Inhibitory regulation of platelets by hydrogen sulphide, 3rd European Conference on the Biology of Hydrogen Sulfide (H2S), Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S14-S15, ISSN: 1089-8603
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- Citations: 1
Smyth E, Emerson M, Nelson M, 2015, The impact of abacavir sulphate and tenofovir on platelet function, HIV MEDICINE, Vol: 16, Pages: 21-21, ISSN: 1464-2662
Emerson M, 2015, Hydrogen Sulfide and Platelets: A Possible Role in Thrombosis, CHEMISTRY, BIOCHEMISTRY AND PHARMACOLOGY OF HYDROGEN SULFIDE, Vol: 230, Pages: 153-162, ISSN: 0171-2004
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- Citations: 13
Apostoli GL, Solomon A, Smallwood MJ, et al., 2014, Role of inorganic nitrate and nitrite in driving nitric oxide-GMP-mediated inhibition of platelet aggregation in vitro and in vivo, Journal of Thrombosis and Haemostasis, Vol: 12, Pages: 1880-1889, ISSN: 1538-7933
BackgroundNitric oxide (NO) is a critical negative regulator of platelets that is implicated in the pathology of thrombotic diseases. Platelets generate NO, but the presence and functional significance of NO synthase (NOS) in platelets is unclear. Inorganic nitrate/nitrite is increasingly being recognized as a source of bioactive NO, although its role in modulating platelets during health and vascular dysfunction is incompletely understood.MethodsWe investigated the functional significance and upstream sources of NO–cGMP signaling events in platelets by using established methods for assessing in vitro and in vivo platelet aggregation, and assessed the bioconversion of inorganic nitrate to nitrite during deficiency of endothelial NOS (eNOS).ResultsThe phosphodiesterase 5 (PDE5) inhibitor sildenafil inhibited human platelet aggregation in vitro. This inhibitory effect was abolished by a guanylyl cyclase inhibitor and NO scavengers, but unaffected by NOS inhibition. Inorganic nitrite drove cGMP-mediated inhibition of human platelet aggregation in vitro and nitrate inhibited platelet function in eNOS−/− mice in vivo in a model of thromboembolic radiolabeled platelet aggregation associated with an enhanced plasma nitrite concentration as compared with wild-type mice.ConclusionsPlatelets generate transient, endogenous cGMP signals downstream of NO that are primarily independent of NOS and may be enhanced by inhibition of PDE5. Furthermore, nitrite can generate transient NO–cGMP signals in platelets. The absence of eNOS leads to enhanced plasma nitrite levels following nitrate administration in vivo, which negatively impacts on platelet function. Our data suggest that inorganic nitrate exerts an antiplatelet effect during eNOS deficiency, and, potentially, that dietary nitrate may reduce platelet hyperactivity during endothelial dysfunction.
Jones CI, Tucker KL, Sasikumar P, et al., 2014, Integrin-linked kinase regulates the rate of platelet activation and is essential for the formation of stable thrombi, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 12, Pages: 1342-1352, ISSN: 1538-7933
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- Citations: 22
Smyth E, Solomon A, Vydyanath A, et al., 2014, Induction and enhancement of platelet aggregation in vitro and in vivo by model polystyrene nanoparticles, Nanotoxicology, Vol: 9, Pages: 356-364, ISSN: 1743-5404
Abstract Nanoparticles (NPs) may come into contact with circulating blood elements including platelets following inhalation and translocation from the airways to the bloodstream or during proposed medical applications. Studies with model polystyrene latex nanoparticles (PLNPs) have shown that NPs are able to induce platelet aggregation in vitro suggesting a poorly defined potential mechanism of increased cardiovascular risk upon NP exposure. We aimed to provide insight into the mechanisms by which NPs may increase cardiovascular risk by determining the impact of a range of concentrations of PLNPs on platelet activation in vitro and in vivo and identifying the signaling events driving NP-induced aggregation. Model PLNPs of varying nano-size (50 and 100 nm) and surface chemistry [unmodified (uPLNP), amine-modified (aPLNP) and carboxyl-modified (cPLNP)] were therefore examined using in vitro platelet aggregometry and an established mouse model of platelet thromboembolism. Most PLNPs tested induced GPIIb/IIIa-mediated platelet aggregation with potencies that varied with both surface chemistry and nano-size. Aggregation was associated with signaling events, such as granule secretion and release of secondary agonists, indicative of conventional agonist-mediated aggregation. Platelet aggregation was associated with the physical interaction of PLNPs with the platelet membrane or internalization. 50 nm aPLNPs acted through a distinct mechanism involving the physical bridging of adjacent non-activated platelets leading to enhanced agonist-induced aggregation in vitro and in vivo. Our study suggests that should they translocate the pulmonary epithelium, or be introduced into the blood, NPs may increase the risk of platelet-driven events by inducing or enhancing platelet aggregation via mechanisms that are determined by their distinct combination of nano-size and surface chemistry.
Emerson M, Solomon A, Smyth E, et al., 2014, Inhibition of platelet aggregation <i>in vitro</i> and <i>in vivo</i> by the H<sub>2</sub>S releasing compound GYY4137, 3rd International Conference on H2S Biology and Medicine, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S47-S47, ISSN: 1089-8603
Kirkby NS, Lundberg MH, Chan MV, et al., 2013, Blockade of the purinergic P2Y<sub>12</sub> receptor greatly increases the platelet inhibitory actions of nitric oxide, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 15782-15787, ISSN: 0027-8424
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- Citations: 48
Ilkan Z, Mustafa F, Apostoli G, et al., 2013, Hydrogen sulfide inhibits human platelet aggregation, 2nd European Conference on the Biology of Hydrogen Sulfide, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S26-S26, ISSN: 1089-8603
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- Citations: 4
Smyth E, Solomon A, Vydyanath A, et al., 2013, The potencies and mechanisms by which engineered nanoparticles induce platelet aggregation are dependent upon their precise physicochemistry, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 895-896, ISSN: 1538-7933
Apostoli G, Solomon A, Emerson M, 2013, Sildenafil reduces platelet activity via both NO synthase and NO synthase-independent pathways, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 445-446, ISSN: 1538-7933
Emerson M, Solomon A, Smyth E, et al., 2013, Role of platelets in driving the thrombotic risk and protective processes associated with exposure to diesel exhaust particles, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 643-644, ISSN: 1538-7933
Gillespie S, O'Malley A, Solomon A, et al., 2013, Anti-aggregatory effects of Sulforaphane on <i>in vitro</i> platelet function, Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB), Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
Solomon A, Smyth E, Mitha N, et al., 2013, Induction of platelet aggregation after a direct physical interaction with diesel exhaust particles, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 11, Pages: 325-334, ISSN: 1538-7933
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- Citations: 21
Kilkenny C, Browne WJ, Cuthill IC, et al., 2012, Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research, OSTEOARTHRITIS AND CARTILAGE, Vol: 20, Pages: 256-260, ISSN: 1063-4584
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- Citations: 454
Holbrook L, Moore C, Sanz-Rosa D, et al., 2012, A NOD/SCID mouse model for the assessment of human platelet aggregation in vivo, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 10, Pages: 490-492, ISSN: 1538-7933
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- Citations: 2
Kilkenny C, Browne WJ, Cuthill IC, et al., 2012, Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research, VETERINARY CLINICAL PATHOLOGY, Vol: 41, Pages: 27-31, ISSN: 0275-6382
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- Citations: 97
Moore C, Emerson M, 2012, Assessment of Platelet Aggregation Responses In Vivo in the Mouse, PLATELETS AND MEGAKARYOCYTES, VOL 3: ADDITIONAL PORTOCOLS AND PERSPECTIVES, Vol: 788, Pages: 21-28, ISSN: 1064-3745
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- Citations: 2
Mohamed TMA, Oceandy D, Zi M, et al., 2011, Plasma Membrane Calcium Pump (PMCA4)-Neuronal Nitric-oxide Synthase Complex Regulates Cardiac Contractility through Modulation of a Compartmentalized Cyclic Nucleotide Microdomain, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 41520-41529, ISSN: 0021-9258
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- Citations: 65
Jones S, Moore C, Emerson M, et al., 2011, Crosstalk between P2X1 and P2Y1 receptors stimulates synergistic calcium responses and promotes adp-mediated platelet aggregation, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 9, Pages: 317-318, ISSN: 1538-7933
Armstrong PC, Kirkby NS, Zain ZN, et al., 2011, Thrombosis is reduced by inhibition of COX-1, but unaffected by inhibition of COX-2, in an acute model of platelet activation in the mouse, PLoS ONE, Vol: 6, ISSN: 1932-6203
Kilkenny C, Browne W, Cuthill IC, et al., 2011, Animal research: reporting <i>in vivo</i> experiments-The ARRIVE Guidelines, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 31, Pages: 991-993, ISSN: 0271-678X
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- Citations: 2799
Moore C, Sanz-Rosa D, Emerson M, 2011, Distinct role and location of the endothelial isoform of nitric oxide synthase in regulating platelet aggregation in males and females <i>in vivo</i>, EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 651, Pages: 152-158, ISSN: 0014-2999
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- Citations: 23
Jones S, Solomon A, Sanz-Rosa D, et al., 2010, The plasma membrane calcium ATPase modulates calcium homeostasis, intracellular signaling events and function in platelets, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 8, Pages: 2766-2774, ISSN: 1538-7933
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- Citations: 17
Solomon A, Jones S, Sanz-Rosa D, et al., 2010, The Plasma Membrane Calcium ATPase Regulates Calcium Homeostasis, Function and Negative Signalling Events in Platelets, CIRCULATION, Vol: 122, ISSN: 0009-7322
Emerson M, 2010, Refinement, reduction and replacement approaches to <i>in vivo</i> cardiovascular research, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 161, Pages: 749-754, ISSN: 0007-1188
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- Citations: 11
Holton M, Mohamed TMA, Oceandy D, et al., 2010, Endothelial nitric oxide synthase activity is inhibited by the plasma membrane calcium ATPase in human endothelial cells, CARDIOVASCULAR RESEARCH, Vol: 87, Pages: 440-448, ISSN: 0008-6363
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- Citations: 38
Moore C, Tymvios C, Emerson M, 2010, Functional regulation of vascular and platelet activity during thrombosis by nitric oxide and endothelial nitric oxide synthase, THROMBOSIS AND HAEMOSTASIS, Vol: 104, Pages: 342-349, ISSN: 0340-6245
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- Citations: 47
Kilkenny C, Browne W, Cuthill IC, et al., 2010, Animal research: Reporting <i>in vivo</i> experiments: The ARRIVE guidelines, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 160, Pages: 1577-1579, ISSN: 0007-1188
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- Citations: 2798
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