Evidence map›Paper›PMID 26988594›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Differential Roles of the NADPH-Oxidase 1 and 2 in Platelet Activation and Thrombosis.

M Keegan Delaney, Kyungho Kim, Brian Estevez, Zheng Xu, Aleksandra Stojanovic-Terpo, Bo Shen, Masuko Ushio-Fukai, Jaehyung Cho, Xiaoping Du

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 3% 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

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Article
  7. Low dose thirdhand smoke exposure enhances platelet functional responses in mice.Experimental biology and medicine (Maywood, N.J.) · 2026
    Article
  8. Redox Control in Platelet Activity and Therapy.Antioxidants (Basel, Switzerland) · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Mechanical Biomimetic Nanocomposites for Multidimensional Treatment of Arterial Thrombosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Oxidative Stress Induced by Cortisol in Human Platelets.International journal of molecular sciences · 2024
    Article
  19. Article
  20. Review

15 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

9 authors at 1 institution in 1 country.

M Keegan DelaneyFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Kyungho KimFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Brian EstevezFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Zheng XuFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Aleksandra Stojanovic-TerpoFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Bo ShenFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Masuko Ushio-FukaiFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Jaehyung ChoFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago.
Xiaoping DuFrom the Departments of Pharmacology (M.K.D., K.K., B.E., Z.X., A.S.-T., B.S., M.U.-F., J.C., X.D.) and Anesthesiology (J.C.), University of Illinois at Chicago. xdu@uic.edu.
University of Illinois Chicago · US

Funding

Signaling mechanisms of platelet GPIb-IXR01HL062350 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2000 to 2017
$6.0M
Outside-in signaling mechanisms of platelet integrin alpha-llb-beta3R01HL080264 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DU, XIAOPING · 2007 to 2019
$4.6M
New Strategies for Treating Septic Vasculopathy Inflammation and ThrombosisR01HL125356 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI BONINI, MARCELO G., DU, XIAOPING · 2014 to 2018
$3.4M
Copper transport protein and inflammatory angiogenesisR01HL116976 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FUKAI, TOHRU, USHIO-FUKAI, MASUKO · 2013 to 2016
$2.9M
Protein disulfide isomerase in neutrophil recruitment and vascular inflammationR01HL109439 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHO, JAEHYUNG · 2011 to 2015
$2.0M
Role of Cysteine Sulfenic Acid Formation in Compartmentalization of VEGF SignalinR21HL112293 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI USHIO-FUKAI, MASUKO · 2013 to 2014
$435k
NHLBI NIH HHS R01 HL062350NHLBI NIH HHS R01 HL080264NHLBI NIH HHS R01 HL109439NHLBI NIH HHS R01 HL116976NHLBI NIH HHS R01 HL125356NHLBI NIH HHS R21 HL112293
6 · The paper itself

Abstract

objectiveReactive oxygen species (ROS) are known to regulate platelet activation; however, the mechanisms of ROS production during platelet activation remain unclear. Platelets express different isoforms of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases (NOXs). Here, we investigated the role of NOX1 and NOX2 in ROS generation and platelet activation using NOX1 and NOX2 knockout mice. APPROACH AND

resultsNOX1(-/Y) platelets showed selective defects in G-protein-coupled receptor-mediated platelet activation induced by thrombin and thromboxane A2 analog U46619, but were not affected in platelet activation induced by collagen-related peptide, a glycoprotein VI agonist. In contrast, NOX2(-/-) platelets showed potent inhibition of collagen-related peptide-induced platelet activation, and also showed partial inhibition of thrombin-induced platelet activation. Consistently, production of ROS was inhibited in NOX1(-/Y) platelets stimulated with thrombin, but not collagen-related peptide, whereas NOX2(-/-) platelets showed reduced ROS generation induced by collagen-related peptide or thrombin. Reduced ROS generation in NOX1/2-deficient platelets is associated with impaired activation of Syk and phospholipase Cγ2, but minimally affected mitogen-activated protein kinase pathways. Interestingly, laser-induced arterial thrombosis was impaired but the bleeding time was not affected in NOX2(-/-) mice. Wild-type thrombocytopenic mice injected with NOX2(-/-) platelets also showed defective arterial thrombosis, suggesting an important role for platelet NOX2 in thrombosis in vivo but not hemostasis.

conclusionsNOX1 and NOX2 play differential roles in different platelet activation pathways and in thrombosis. ROS generated by these enzymes promotes platelet activation via the Syk/phospholipase Cγ2/calcium signaling pathway.

Indexed as

Platelet ActivationAnimalsBlood PlateletsCalcium SignalingCD11b AntigenDisease Models, AnimalEnzyme ActivationGenetic Predisposition to DiseaseHemostasisMaleMembrane GlycoproteinsMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesNADH, NADPH OxidoreductasesNADPH Oxidase 1CD11b AntigenCybb protein, mouseMembrane GlycoproteinsMitogen-Activated Protein KinasesNADH, NADPH OxidoreductasesNADPH Oxidase 1NADPH Oxidase 2NADPH OxidasesNOX1 protein, mousePhospholipase C gammaPlatelet Membrane Glycoproteinsplatelet membrane glycoprotein VIReactive Oxygen SpeciesReceptors, G-Protein-CoupledSyk KinaseSyk protein, mouseThrombinblood plateletsNADPH oxidaseplatelet activationreactive oxygen speciesthrombosis

Identifiers

PMID26988594
PMCPMC4850088
OpenAlexW2298142163

What OpenQuestion holds

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Registered trials

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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.