Evidence map›Paper›PMID 19943878›Full record

ArticleJournal of thrombosis and haemostasis : JTH2010

VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA.

A A Kondkar, M S Bray, S M Leal, S Nagalla, D J Liu, Y Jin, J F Dong, Q Ren, S W Whiteheart, C Shaw and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

83 citing papers in PubMed, 196 citations in OpenAlex.

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  10. Unveiling Atherosclerotic Plaque Heterogeneity and SPP1Journal of inflammation research · 2024
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23 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

11 authors at 4 institutions in 1 country.

A A KondkarThomas Jefferson University, The Cardeza Foundation for Hematologic Research and the Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107, USA.
M S Bray
S M Leal
S Nagalla
D J Liu
Y Jin
J F Dong
Q Ren
S W Whiteheart
C Shaw
P F Bray
Baylor College of Medicine · USThomas Jefferson University · USUniversity of Kentucky · USChildren's Nutrition Research Center at Baylor College of Medicine · US

Funding

MOLECULAR MECHANISMS OF PLATELET EXOCYTOSISR01HL056652 · NHLBI · UNIVERSITY OF KENTUCKY · PI WHITEHEART, SIDNEY WALDO · 1996 to 2019
$5.2M
Variation in platelet function: the genetics of platelet gene expressionR01HL102482 · NHLBI · UNIVERSITY OF UTAH · PI BRAY, PAUL F. · 2010 to 2018
$4.6M
Identifying genes regulating platelet reactivityR01HL088458 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI BRAY, PAUL F. · 2007 to 2011
$2.2M
ADVANCED LINKAGE ANALYSIS COURSEST15HG000016 · NHGRI · ROCKEFELLER UNIVERSITY · PI LEAL, SUZANNE M · 1991 to 2013
$1.1M
PHENOTYPES AND GENETIC ANALYSIS OF COMPLEX TRAITSR13MH059864 · NIMH · ROCKEFELLER UNIVERSITY · PI LEAL, SUZANNE MARGARET · 1999 to 1999
–
NHGRI NIH HHS T15 HG000016NHLBI NIH HHS HL88458NHLBI NIH HHS R01 HL056652NHLBI NIH HHS R01 HL088458NHLBI NIH HHS R01 HL102482NIMH NIH HHS R13 MH059864
6 · The paper itself

Abstract

backgroundVariation in platelet reactivity contributes to disorders of hemostasis and thrombosis, but the molecular mechanisms are not well understood.

objectivesTo discover associations between interindividual platelet variability and the responsible platelet genes, and to begin to define the molecular mechanisms altering platelet gene expression. SUBJECTS/

methodsTwo hundred and eighty-eight healthy subjects were phenotyped for platelet responsiveness. Platelet RNA from subjects demonstrating hyperreactivity (n=18) and hyporeactivity (n=11) was used to screen the human transcriptome.

resultsDistinctly different mRNA profiles were observed between subjects with differing platelet reactivity. Increased levels of mRNA for VAMP8/endobrevin, a critical v-SNARE involved in platelet granule secretion, were associated with platelet hyperreactivity (Q=0.0275). Validation studies of microarray results showed 4.8-fold higher mean VAMP8 mRNA levels in hyperreactive than hyporeactive platelets (P=0.0023). VAMP8 protein levels varied 13-fold among platelets from these normal subjects, and were 2.5-fold higher in hyperreactive platelets (P=0.05). Among our cohort of 288 subjects, a VAMP8 single-nucleotide polymorphism (rs1010) was associated with platelet reactivity in an age-dependent manner (P<0.003). MicroRNA-96 was predicted to bind to the 3'-untranslated regionof VAMP8 mRNA and was detected in platelets. Overexpression of microRNA-96 in VAMP8-expressing cell lines caused a dose-dependent decrease in VAMP8 protein and mRNA, suggesting a role in VAMP8 mRNA degradation.

conclusionsThese findings support a role for VAMP8/endobrevin in the heterogeneity of platelet reactivity, and suggest a role for microRNA-96 in the regulation of VAMP8 expression.

Indexed as

Polymorphism, Single Nucleotide3' Untranslated RegionsAdultAge FactorsBinding SitesBlood PlateletsEpinephrineFemaleGene Expression ProfilingGenotypeHCT116 CellsHumansMaleMicroRNAsOligonucleotide Array Sequence AnalysisPhenotype3' Untranslated RegionsEpinephrineMicroRNAsMIRN96 microRNA, humanRNA, MessengerR-SNARE ProteinsVAMP8 protein, human

Identifiers

PMID19943878
PMCPMC3312605
OpenAlexW2165387925

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.