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dc.contributor.authorPula, Giordano
dc.date.accessioned2020-11-30T15:34:03Z
dc.date.available2020-11-30T15:34:03Z
dc.date.issued2019-09
dc.identifier.citationVara D et al. A novel combinatorial technique for simultaneous quantification of oxygen radicals and aggregation reveals unexpected redox patterns in the activation of platelets by different physiopathological stimuli. Haematologica. 2019 Sep;104(9):1879-1891. doi: 10.3324/haematol.2018.208819. Epub 2019 Jan 24.en_US
dc.identifier.pmid30679320
dc.identifier.doi10.3324/haematol.2018.208819
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621583
dc.description.abstracthe regulation of platelets by oxidants is critical for vascular health and may explain thrombotic complications in diseases such as diabetes and dementia, but remains poorly understood. Here, we describe a novel technique combining electron paramagnetic resonance spectroscopy and turbidimetry, which has been utilized to monitor simultaneously platelet activation and oxygen radical generation. This technique has been used to investigate the redox-dependence of human and mouse platelets. Using selective peptide inhibitors of NADPH oxidases (NOXs) on human platelets and genetically modified mouse platelets (NOX1-/- or NOX2-/-), we discovered that: 1) intracellular but not extracellular superoxide anion generated by NOX is critical for platelet activation by collagen; 2) superoxide dismutation to hydrogen peroxide is required for thrombin-dependent activation; 3) NOX1 is the main source of oxygen radicals in response to collagen, while NOX2 is critical for activation by thrombin; 4) two platelet modulators, namely oxidized low density lipoproteins (oxLDL) and amyloid peptide β (Aβ), require activation of both NOX1 and NOX2 to pre-activate platelets. This study provides new insights into the redox dependence of platelet activation. It suggests the possibility of selectively inhibiting platelet agonists by targeting either NOX1 (for collagen) or NOX2 (for thrombin). Selective inhibition of either NOX1 or NOX2 impairs the potentiatory effect of tested platelet modulators (oxLDL and Aβ), but does not completely abolish platelet hemostatic function. This information offers new opportunities for the development of disease-specific antiplatelet drugs with limited bleeding side effects by selectively targeting one NOX isoenzyme.en_US
dc.language.isoenen_US
dc.publisherPagepress Publicationsen_US
dc.relation.urlhttps://doi.org/10.3324/haematol.2018.208819en_US
dc.rights©2019 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.en_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectPlatelet Aggregationen_US
dc.subjectPlatelet Activationen_US
dc.subjectOxidation-Reductionen_US
dc.subjectReactive Oxygen Speciesen_US
dc.subjectSuperoxidesen_US
dc.subjectThrombosisen_US
dc.subjectHydrogen Peroxideen_US
dc.subjectCombinatorial Chemistry Techniquesen_US
dc.subjectElectron Spin Resonance Spectroscopyen_US
dc.subjectBlood Plateletsen_US
dc.subjectAnionsen_US
dc.titleA novel combinatorial technique for simultaneous quantification of oxygen radicals and aggregation reveals unexpected redox patterns in the activation of platelets by different physiopathological stimulien_US
dc.typeJournal Articleen_US
dc.identifier.journalHaematologicaen_US
dc.identifier.pmcidPMC6717585
dc.description.noteThis article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.en_US
dc.description.fundingPG/15/40/31522/British Heart Foundation/United Kingdom R01 HL079207/HL/NHLBI NIH HHS/United States R01 HL112914/HL/NHLBI NIH HHS/United Statesen_US
dc.type.versionPublisheden_US


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©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright.  All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions https://creativecommons.org/licenses/by-nc/4.0/legalcode.
Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions:
https://creativecommons.org/licenses/by-nc/4.0/legalcode,
sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
Except where otherwise noted, this item's license is described as ©2019 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.