Evidence map›Paper›PMID 37875382›Full record

ArticleJournal of thrombosis and haemostasis : JTH2023

Factor VIIa releases phosphatidylserine-enriched extracellular vesicles from endothelial cells by activating acid sphingomyelinase.

Kaushik Das, Shiva Keshava, Tanmoy Mukherjee, Jue Wang, Jhansi Magisetty, 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, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed, 13 citations in OpenAlex.

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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

8 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, TX, USA. Electronic address: Kaushik.Das@uthct.edu.
Shiva KeshavaDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX, USA.
Tanmoy MukherjeeDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX, USA.
Jue WangDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX, USA.
Jhansi MagisettyDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX, USA.
Richard KolesnickMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Usha R PendurthiDepartment of Cellular and Molecular Biology, UT Tyler School of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX, 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, TX, USA. Electronic address: Vijay.Rao@uthct.edu.
The University of Texas at Tyler · USMemorial Sloan Kettering Cancer Center · US

Funding

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
NHLBI NIH HHS R01 HL107483NHLBI NIH HHS R01 HL124055
6 · The paper itself

Abstract

backgroundOur recent studies showed that activated factor (F) VII (FVIIa) releases extracellular vesicles (EVs) from the endothelium. FVIIa-released EVs were found to be enriched with phosphatidylserine (PS) and contribute to the hemostatic effect of FVIIa in thrombocytopenia and hemophilia.

objectiveTo investigate mechanisms by which FVIIa induces EV biogenesis and enriches EVs with PS.

methodsFVIIa activation of acid sphingomyelinase (aSMase) was evaluated by its translocation to the cell surface. The role of aSMase in the biogenesis of FVIIa-induced EVs and their enrichment with PS was investigated using specific siRNAs and inhibitors of aSMase and its downstream metabolites. Wild-type and aSMase

resultsFVIIa activation of aSMase is responsible for both the externalization of PS and the release of EVs in endothelial cells. FVIIa-induced aSMase activation led to ceramide generation and de novo expression of transmembrane protein 16F. Inhibitors of ceramidases, sphingosine kinase, or sphingosine-1-phosphate receptor modulator blocked FVIIa-induced expression of transmembrane protein 16F and PS externalization without interfering with FVIIa release of EVs. In vivo, FVIIa release of EVs was markedly impaired in aSMase

conclusionOur study identifies a novel mechanism by which FVIIa induces PS externalization and releases PS-enriched EVs.

Indexed as

Extracellular VesiclesHemostaticsThrombocytopeniaAnimalsEndothelial CellsFactor VIIaMicePhosphatidylserinesSphingomyelin PhosphodiesteraseASMase, mouseFactor VIIaHemostaticsPhosphatidylserinesSphingomyelin Phosphodiesteraseacid sphingomyelinaseextracellular vesiclesfactor VIIahemostasisphosphatidylserine

Identifiers

PMID37875382
PMCPMC11770839
OpenAlexW4387860298

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.