Evidence map›Paper›PMID 26264622›Full record

ArticleJournal of thrombosis and haemostasis : JTH2015

A novel pathway of cellular activation mediated by antiphospholipid antibody-induced extracellular vesicles.

M Wu, J Barnard, S Kundu, K R McCrae

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

28 citing papers in PubMed, 47 citations in OpenAlex.

  1. Trial
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  7. Article
  8. Antiphospholipid Syndrome in Pregnancy: New and Old Pathogenetic Mechanisms.International journal of molecular sciences · 2023
    Review
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  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
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  17. Article
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  19. Potential of miRNAs to predict and treat inflammation from the perspective of Familial Mediterranean Fever.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

M WuDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA.
J BarnardQuantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
S KunduDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA.
K R McCraeDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA.
Cleveland Clinic · US

Funding

ROLE OF MICROPARTICLES IN THE ANTI-PHOSPHOLIPID SYNDROMEP50HL081011 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS · 2006 to 2010
$12.9M
Transcriptional control of endothelium in APS by Kruppel Like factorsR01HL123098 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI JAIN, MUKESH KUMAR, MCCRAE, KEITH R. · 2014 to 2017
$1.8M
NHLBI NIH HHS P50 HL081011NHLBI NIH HHS R01 HL123098
6 · The paper itself

Abstract

backgroundElevated levels of endothelial cell (EC)-derived extracellular vesicles (EVs) circulate in patients with antiphospholipid antibodies (APLAs), and APLAs, particularly those against β2 -glycoprotein I (β2 GPI), stimulate EV release from ECs. However, the effects of EC-derived EVs have not been characterized.

objectiveTo determine the mechanism by which EVs released from ECs by anti-β2 GPI antibodies activate unstimulated ECs. PATIENTS/

methodsWe used interleukin (IL)-1 receptor inhibitors, small interfering RNA (siRNA) against Toll-like receptors (TLRs) and microRNA (miRNA) profiling to assess the mechanism(s) by which EVs released from ECs exposed to anti-β2 GPI antibodies activated unstimulated ECs. RESULTS AND

conclusionsAnti-β2 GPI antibodies caused formation of an EC inflammasome and the release of EVs that were enriched in mature IL-1β, had a distinct miRNA profile, and caused endothelial activation. However, activation was not inhibited by an IL-1β antibody, an IL-1 receptor antagonist, or IL-1 receptor siRNA. EC activation by EVs required IL-1 receptor-associated kinase 4 phosphorylation, and was inhibited by pretreatment of cells with TLR7 siRNA or RNase A, which degrades ssRNA. Profiling of miRNA in EVs released from ECs incubated with β2 GPI and either control IgG or anti-β2 GPI antibodies revealed numerous differences in the content of specific miRNAs, including a significant decrease in mIR126. These observations demonstrate that, although anti-β2 GPI-derived endothelial EVs contain IL-1β, they activate unstimulated ECs through a TLR7-dependent and ssRNA-dependent pathway. Alterations in miRNA content may contribute to the ability of EVs derived from ECs exposed to anti-β2 GPI antibodies to activate unstimulated ECs in an autocrine or paracrine manner.

Indexed as

Antibodies, AntiphospholipidAntiphospholipid Syndromebeta 2-Glycoprotein ICells, CulturedEndothelial CellsExtracellular VesiclesFemaleHumansInflammasomesInterleukin-1betaMaleMicroRNAsMiddle AgedReceptors, Interleukin-1RNA InterferenceSignal TransductionAntibodies, Antiphospholipidbeta 2-Glycoprotein IIL1B protein, humanInflammasomesInterleukin-1betaMicroRNAsReceptors, Interleukin-1TLR7 protein, humanToll-Like Receptor 7antiphospholipid antibodiescell-derived microparticlesendothelial cellsexosomesinterleukinsToll-like receptors

Identifiers

PMID26264622
PMCPMC4877623
OpenAlexW1954743756

What OpenQuestion holds

Textmetadata
LicenceTDM
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.