Evidence map›Paper›PMID 37926194›Full record

ArticleJournal of thrombosis and haemostasis : JTH2024

MicroRNA-10a enrichment in factor VIIa-released endothelial extracellular vesicles: potential mechanisms.

Kaushik Das, Shiva Keshava, Richard Kolesnick, Usha R Pendurthi, L Vijaya Mohan Rao

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

Article in Journal of thrombosis and haemostasis : JTH, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Kaushik DasDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, the University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
Shiva KeshavaDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, the University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
Richard KolesnickMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Usha R PendurthiDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, the University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
L Vijaya Mohan RaoDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, the University of Texas Health Science Center at Tyler, Tyler, Texas, USA. Electronic address: Vijay.Rao@uthct.edu.
The University of Texas at Tyler · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Membrane Phospholipids: The Key Regulators of Tissue Factor Encryption/DecryptionR01HL124055 · NHLBI · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · PI LELLA, VIJAYA MOHAN RAO · 2015 to 2023
$3.3M
Factor VIIa Interaction with Endothelial Cell Protein C ReceptorR01HL107483 · NHLBI · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · PI LELLA, VIJAYA MOHAN RAO · 2012 to 2019
$2.9M
NCI NIH HHS P30 CA008748NHLBI NIH HHS R01 HL107483NHLBI NIH HHS R01 HL124055
6 · The paper itself

Abstract

backgroundFactor VIIa induces the release of extracellular vesicles (EVs) from endothelial cells (EEVs). Factor VIIa-released EEVs are enriched with microRNA-10a (miR10a) and elicit miR10a-dependent cytoprotective responses.

objectivesTo investigate mechanisms by which FVIIa induces miR10a expression in endothelial cells and sorts miR10a into the EVs.

methodsActivation of Elk-1 and TWIST1 expression was analyzed by immunofluorescence microscopy and immunoblot analysis. Small interfering RNA silencing approach was used to knock down the expression of specific genes in endothelial cells. EVs secreted from endothelial cells or released into circulation in mice were isolated by centrifugation and quantified by nanoparticle tracking analysis. Factor VIIa or EVs were injected into mice; mice were challenged with lipopolysaccharides to assess the cytoprotective effects of FVIIa or EVs.

resultsFVIIa activation of ERK1/2 triggered the activation of Elk-1, which led to the induction of TWIST1, a key transcription factor involved in miR10a expression. Factor VIIa also induced the expression of La, a small RNA-binding protein. Factor VIIa-driven acid sphingomyelinase (ASM) activation and the subsequent activation of the S1P receptor pathway were responsible for the induction of La. Silencing of ASM or La significantly reduced miR10a levels in FVIIa-released EEVs without affecting the cellular expression of miR10a. Factor VIIa-EEVs from ASM knocked-down cells failed to provide cytoprotective responses in cell and murine model systems. Administration of FVIIa protected wild-type but not ASM

conclusionOur data suggest that enhanced cellular expression of miR10a coupled with La-dependent sorting of miR10a is responsible for enriching FVIIa-released EVs with miR10a.

Indexed as

Extracellular VesiclesMicroRNAsAnimalsEndothelial CellsFactor VIIaLipopolysaccharidesMiceSignal TransductionFactor VIIaLipopolysaccharidesMicroRNAscytoprotectionextracellular vesiclesfactor VIIainflammationmicroRNAsRNA transport

Identifiers

PMID37926194
PMCPMC10872460
OpenAlexW4388342110

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.