Evidence map›Paper›PMID 24494191›Full record

ArticleRedox biology2014

The role of Nox1 and Nox2 in GPVI-dependent platelet activation and thrombus formation.

T G Walsh, M C Berndt, N Carrim, J Cowman, D Kenny, P Metharom

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 102 citations in OpenAlex.

  1. Review
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  5. Redox Control in Platelet Activity and Therapy.Antioxidants (Basel, Switzerland) · 2025
    Review
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  7. Article
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  17. Review
  18. Redox Mechanisms of Platelet Activation in Aging.Antioxidants (Basel, Switzerland) · 2022
    Review
  19. Article
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

T G WalshDepartment of Experimental Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
M C BerndtDepartment of Experimental Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland ; Faculty of Health Sciences, Curtin University, Perth, Australia.
N CarrimDepartment of Experimental Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
J CowmanDepartment of Molecular Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
D KennyDepartment of Molecular Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
P MetharomDepartment of Experimental Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland ; Faculty of Health Sciences, Curtin University, Perth, Australia.
Royal College of Surgeons in Ireland · IECurtin University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundActivation of the platelet-specific collagen receptor, glycoprotein (GP) VI, induces intracellular reactive oxygen species (ROS) production; however the relevance of ROS to GPVI-mediated platelet responses remains unclear.

objectiveThe objective of this study was to explore the role of the ROS-producing NADPH oxidase (Nox)1 and 2 complexes in GPVI-dependent platelet activation and collagen-induced thrombus formation. METHODS AND

resultsROS production was measured by quantitating changes in the oxidation-sensitive dye, H2DCF-DA, following platelet activation with the GPVI-specific agonist, collagen related peptide (CRP). Using a pharmacological inhibitor specific for Nox1, 2-acetylphenothiazine (ML171), and Nox2 deficient mice, we show that Nox1 is the key Nox homolog regulating GPVI-dependent ROS production. Nox1, but not Nox2, was essential for CRP-dependent thromboxane (Tx)A2 production, which was mediated in part through p38 MAPK signaling; while neither Nox1 nor Nox2 was significantly involved in regulating CRP-induced platelet aggregation/integrin αIIbβ3 activation, platelet spreading, or dense granule and α-granule release (ATP release and P-selectin surface expression, respectively). Ex-vivo perfusion analysis of mouse whole blood revealed that both Nox1 and Nox2 were involved in collagen-mediated thrombus formation at arterial shear.

conclusionTogether these results demonstrate a novel role for Nox1 in regulating GPVI-induced ROS production, which is essential for optimal p38 activation and subsequent TxA2 production, providing an explanation for reduced thrombus formation following Nox1 inhibition.

Indexed as

Platelet ActivationAnimalsArteriesCarrier ProteinsFluoresceinsMAP Kinase Signaling SystemMembrane GlycoproteinsMiceNADH, NADPH OxidoreductasesNADPH Oxidase 1NADPH Oxidase 2NADPH OxidasesPeptidesPhenothiazinesPlatelet Membrane GlycoproteinsReactive Oxygen Species2',7'-dichlorodihydrofluorescein diacetate2-acetylphenothiazineCarrier Proteinscollagen-related peptideCybb protein, mouseFluoresceinsMembrane GlycoproteinsNADH, NADPH OxidoreductasesNADPH Oxidase 1NADPH Oxidase 2NADPH OxidasesNOX1 protein, mousePeptidesPhenothiazinesPlatelet Membrane Glycoproteinsplatelet membrane glycoprotein VIReactive Oxygen SpeciesThromboxane A2Glycoprotein VINAPDH oxidasePlateletsReactive oxygen speciesThrombus

Identifiers

PMID24494191
PMCPMC3909778
OpenAlexW2167383935

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.