74 results found
Rauzi F, Smyth E, Emerson M, 2017, Refinement of Mouse Protocols for the Study of Platelet Thromboembolic Responses In Vivo., Thromb Haemost, Vol: 117, Pages: 2283-2290
Smyth E, Solomon A, Birrell MA, et al., 2017, Influence of inflammation and nitric oxide upon platelet aggregation following deposition of diesel exhaust particles in the airways., British Journal of Pharmacology, Vol: 174, Pages: 2130-2139, ISSN: 0007-1188
Background and Purpose: Exposure to nanoparticulate pollution has been implicated in platelet-driven thrombotic events such as myocardial infarction. Inflammation and impairment of NO bioavailability have been proposed as potential causative mechanisms. It is unclear, however, whether airways exposure to combustion-derived nanoparticles such as diesel exhaust particles (DEP) or carbon black (CB) can augment platelet aggregation in vivo and the underlying mechanisms remain undefined. We aimed to investigate the effects of acute lung exposure to DEP and CB on platelet activation and the associated role of inflammation and endothelial-derived NO.Experimental Approach: DEP and CB were intratracheally instilled into wild-type (WT) and eNOS−/− mice and platelet aggregation was assessed in vivo using an established model of radio-labelled platelet thromboembolism. The underlying mechanisms were investigated by measuring inflammatory markers, NO metabolites and light transmission aggregometry.Key Results: Platelet aggregation in vivo was significantly enhanced in WT and eNOS−/− mice following acute airways exposure to DEP but not CB. CB exposure, but not DEP, was associated with significant increases in pulmonary neutrophils and IL-6 levels in the bronchoalveolar lavage fluid and plasma of WT mice. Neither DEP nor CB affected plasma nitrate/nitrite concentration and DEP-induced human platelet aggregation was inhibited by an NO donor.Conclusions and Implications: Pulmonary exposure to DEP and subsequent platelet activation may contribute to the reports of increased cardiovascular risk, associated with exposure to airborne pollution, independent of its effects on inflammation or NO bioavailability.
Smyth E, Solomon A, Birrell MA, et al., 2017, Response to 'Effects of diesel exhaust particles on coagulation', BRITISH JOURNAL OF PHARMACOLOGY, Vol: 174, Pages: 4200-4200, ISSN: 0007-1188
Emerson M, 2015, Hydrogen Sulfide and Platelets: A Possible Role in Thrombosis., Handb Exp Pharmacol, Vol: 230, Pages: 153-162, ISSN: 0171-2004
Platelets are circulating blood elements with key roles in haemostasis and thrombosis. Platelets are activated by a range of stimuli including exposed subendothelial components. Haemostasis also depends upon the effects of inhibitory substances, including the gasotransmitter nitric oxide whose effects on platelets are well documented. Evidence is also emerging to suggest that H2S is generated enzymatically by platelets and can impact their function. Exposure of platelets to H2S from slow-release compounds inhibits aggregation and exerted anti-thrombotic effects in vivo. The mechanisms by which H2S impacts platelet function and the importance of interactions between H2S and other gasotransmitters remain unclear. H2S is therefore emerging as a potentially important regulator of platelet activation and thrombosis. Further study is required to evaluate its importance as a regulator of platelet physiology and associated pathological conditions such as myocardial infarction and stroke.
Emerson M, Ahmad O, Rauzi F, et al., 2015, Physiological regulation of platelet aggregation by the gasotransmitter hydrogen sulfide, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 13, Pages: 406-406, 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
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
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
Smyth E, Solomon A, Vydyanath A, et al., 2015, Induction and enhancement of platelet aggregation in vitro and in vivo by model polystyrene nanoparticles, NANOTOXICOLOGY, Vol: 9, Pages: 356-364, ISSN: 1743-5390
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.
Emerson M, Solomon A, Smyth E, et al., 2014, Inhibition of platelet aggregation in vitro and in vivo by the H2S releasing compound GYY4137, 3rd International Conference on H2S Biology and Medicine, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S47-S47, ISSN: 1089-8603
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
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 in vitro platelet function, Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB), Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
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
Kirkby NS, Lundberg MH, Chan MV, et al., 2013, Blockade of the purinergic P2Y(12) 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
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
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
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
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
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
Moore C, Emerson M, 2012, Assessment of platelet aggregation responses in vivo in the mouse., Methods Mol Biol, Vol: 788, Pages: 21-28
Platelet aggregation responses are conventionally assessed in cuvette-based systems using either isolated platelets or whole blood. Unfortunately, in vitro aggregometry poorly predicts in vivo functionality, since mediators derived from the vascular endothelium are major regulators of platelet function. There is a need, therefore, for functional assays that assess platelet responsiveness in vivo in the presence of an intact and functional vascular endothelium. We have developed methodology for monitoring aggregation responses of freely circulating radiolabelled platelets using external detection probes in the anaesthetised mouse. Intravenous injection of platelet agonists induces reversible, dose-dependent aggregation responses that are sensitive to anti-platelet therapies and modification of the vascular endothelium. The technique provides a means of determining the effects of pharmacological and genetic manipulation upon platelet function in vivo.
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
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
Kilkenny C, Browne W, Cuthill IC, et al., 2011, Animal research: reporting in vivo experiments-The ARRIVE Guidelines, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 31, Pages: 991-993, ISSN: 0271-678X
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
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 in vivo, EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 651, Pages: 152-158, ISSN: 0014-2999
Emerson M, 2010, Kv1.3: The perfect opening of the platelet voltage gate, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 588, Pages: 1809-1809, ISSN: 0022-3751
Emerson M, 2010, Refinement, reduction and replacement approaches to in vivo cardiovascular research, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 161, Pages: 749-754, ISSN: 0007-1188
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