Evidence map›Paper›PMID 27609643›Full record

Trial reportBlood2016

Platelet WDR1 suppresses platelet activity and is associated with cardiovascular disease.

Emilie Montenont, Christina Echagarruga, Nicole Allen, Elisa Araldi, Yajaira Suarez, Jeffrey S Berger

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

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

  1. Pooled it
  2. Trial
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  8. Observational
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  10. Review
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  14. Review
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  17. Article
  18. An Insight into Recent Advances on Platelet Function in Health and Disease.International journal of molecular sciences · 2022
    Review
  19. Article
  20. Article
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 1 country.

Emilie MontenontDivisions of Cardiology and Hematology, Department of Medicine, New York University School of Medicine, New York, NY.
Christina EchagarrugaDivisions of Cardiology and Hematology, Department of Medicine, New York University School of Medicine, New York, NY.
Nicole AllenDivisions of Cardiology and Hematology, Department of Medicine, New York University School of Medicine, New York, NY.
Elisa AraldiSection of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT; and.
Yajaira SuarezSection of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT; and.
Jeffrey S BergerDivisions of Cardiology and Hematology, Department of Medicine, New York University School of Medicine, New York, NY.
New York University · USYale University · US

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MEGAN C KING · 1985 to 2026
$85.0M
Platelet Activity & Cardiovascular Events following Vascular SurgeryR01HL114978 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BERGER, JEFFREY S · 2013 to 2017
$3.0M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA016359NHLBI NIH HHS R01 HL114978
6 · The paper itself

Abstract

Platelet activity plays a major role in hemostasis with increased platelet activity likely contributing to the pathogenesis of atherothrombosis. We sought to identify associations between platelet activity variability and platelet-related genes in healthy controls. Transcriptional profiling of platelets revealed that WD-40 repeat domain 1 (WDR1), an enhancer of actin-depolymerizing factor activity, is downregulated in platelet messenger RNA (mRNA) from subjects with a hyperreactive platelet phenotype. We used the human megakaryoblastic cell line MEG-01 as an in vitro model for human megakaryocytes and platelets. Stimulation of MEG-01 with thrombin reduced levels of WDR1 transcripts and protein. WDR1 knockdown (KD) in MEG-01 cells increased adhesion and spreading in both the basal and activated states, increased F-actin content, and increased the basal intracellular calcium concentration. Platelet-like particles (PLPs) produced by WDR1 KD cells were fewer in number but larger than PLPs produced from unmodified MEG-01 cells, and had significantly increased adhesion in the basal state and upon thrombin activation. In contrast, WDR1 overexpression reversed the WDR1 KD phenotype of megakaryocytes and PLPs. To translate the clinical significance of these findings, WDR1 expression was measured in platelet RNA from subjects with established cardiovascular disease (n = 27) and age- and sex-matched controls (n = 10). The WDR1 mRNA and protein level was significantly lower in subjects with cardiovascular disease. These data suggest that WDR1 plays an important role in suppressing platelet activity, where it alters the actin cytoskeleton dynamics, and downregulation of WDR1 may contribute to the platelet-mediated pathogenesis of cardiovascular disease.

Indexed as

Gene Expression RegulationPlatelet AdhesivenessAdultAtherosclerosisBlood PlateletsCell LineCytoskeletonFemaleHumansMaleMegakaryocytesMicrofilament ProteinsMicrofilament ProteinsWDR1 protein, human

Identifiers

PMID27609643
PMCPMC5073182
OpenAlexW2509570419

What OpenQuestion holds

Textmetadata
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.