Evidence map›Paper›PMID 30560697›Full record

ArticlePlatelets2019

Protease-activated receptor 4 activity promotes platelet granule release and platelet-leukocyte interactions.

Rachel A Rigg, Laura D Healy, Tiffany T Chu, Anh T P Ngo, Annachiara Mitrugno, Jevgenia Zilberman-Rudenko, Joseph E Aslan, Monica T Hinds, Lisa Dirling Vecchiarelli, Terry K Morgan and 6 more

Open access · greenAbstract read
In one paragraph

Article in Platelets, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
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  14. Targeting PAR4 to Reduce Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2023
    Article
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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

16 authors at 2 institutions in 1 country.

Rachel A Rigga Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Laura D Healyb Department of Cell, Developmental & Cancer Biology , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Tiffany T Chua Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Anh T P Ngoa Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.ORCID http://orcid.org/0000-0002-2179-6584
Annachiara Mitrugnoa Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Jevgenia Zilberman-Rudenkoa Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Joseph E Asland Department of Biochemistry and Molecular Biology , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Monica T Hindsa Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Lisa Dirling Vecchiarellif Department of Pathology , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Terry K Morganf Department of Pathology , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
András Grubera Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Kayla J Templeg Department of Pharmacology , Vanderbilt University School of Medicine , Nashville , TN , USA.
Craig W Lindsleyg Department of Pharmacology , Vanderbilt University School of Medicine , Nashville , TN , USA.
Matthew T Duvernayg Department of Pharmacology , Vanderbilt University School of Medicine , Nashville , TN , USA.
Heidi E Hammg Department of Pharmacology , Vanderbilt University School of Medicine , Nashville , TN , USA.
Owen J T McCartya Department of Biomedical Engineering , School of Medicine, Oregon Health & Science University , Portland , OR , USA.
Oregon Health & Science University · USVanderbilt University · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Characterization of Coagulation Factor-platelet Interactions: Role of FXIR01HL101972 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Owen J McCarty · 2010 to 2026
$8.5M
INTERACTIONS AT THE MICROBE/HOST INTERFACET32AI007472 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI LANDFEAR, SCOTT M · 1995 to 2019
$6.7M
Targeting PAR4 in Thrombotic Disorders:Pharmacogenomic ApproachR01HL133923 · NHLBI · VANDERBILT UNIVERSITY · PI HAMM, HEIDI E · 2017 to 2020
$2.3M
FXI and SepsisR01GM116184 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI LUPU, FLOREA, MCCARTY, OWEN J · 2015 to 2018
$1.9M
Role of FXI in Thrombohemorrhagic ComplicationsF31HL136230 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ZILBERMAN-RUDENKO, JEVGENIA · 2017 to 2020
$161k
NHLBI NIH HHS F31 HL136230NHLBI NIH HHS R01 HL101972NHLBI NIH HHS R01 HL133923NIAID NIH HHS T32 AI007472NIGMS NIH HHS R01 GM116184NIH HHS P51 OD011092
6 · The paper itself

Abstract

Human platelets express two protease-activated receptors (PARs), PAR1 (F2R) and PAR4 (F2RL3), which are activated by a number of serine proteases that are generated during pathological events and cause platelet activation. Recent interest has focused on PAR4 as a therapeutic target, given PAR4 seems to promote experimental thrombosis and procoagulant microparticle formation, without a broadly apparent role in hemostasis. However, it is not yet known whether PAR4 activity plays a role in platelet-leukocyte interactions, which are thought to contribute to both thrombosis and acute or chronic thrombo-inflammatory processes. We sought to determine whether PAR4 activity contributes to granule secretion from activated platelets and platelet-leukocyte interactions. We performed in vitro and ex vivo studies of platelet granule release and platelet-leukocyte interactions in the presence of PAR4 agonists including PAR4 activating peptide, thrombin, cathepsin G, and plasmin in combination with small-molecule PAR4 antagonists. Activation of human platelets with thrombin, cathepsin G, or plasmin potentiated platelet dense granule secretion that was specifically impaired by PAR4 inhibitors. Platelet-leukocyte interactions and platelet P-selectin exposure the following stimulation with PAR4 agonists were also impaired by activated PAR4 inhibition in either a purified system or in whole blood. These results indicate PAR4-specific promotion of platelet granule release and platelet-leukocyte aggregate formation and suggest that pharmacological control of PAR4 activity could potentially attenuate platelet granule release or platelet-leukocyte interaction-mediated pathological processes.

Indexed as

Cell CommunicationAnimalsBiomarkersBlood PlateletsCytoplasmic GranulesFlow CytometryHumansLeukocytesMalePapioPlatelet ActivationPlatelet AggregationReceptors, ThrombinBiomarkersprotease-activated receptor 4Receptors, ThrombingranulocytesPAR4platelet activationplatelet dense granule releaseplatelet-leukocyte interactionsprotease-activated receptor 4

Identifiers

PMID30560697
PMCPMC6397092
OpenAlexW2904545963

What OpenQuestion holds

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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.