Evidence map›Paper›PMID 25881103›Full record

ArticleThrombosis and haemostasis2015

NMMHC IIA inhibition impedes tissue factor expression and venous thrombosis via Akt/GSK3β-NF-κB signalling pathways in the endothelium.

Kefeng Zhai, Youmei Tang, Yuanyuan Zhang, Fang Li, Yan Wang, Zhengyu Cao, Jun Yu, Junping Kou, Boyang Yu

Erratum issuedAbstract read
In one paragraph

Article in Thrombosis and haemostasis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 45 citations in OpenAlex.

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  15. Function ofFrontiers in microbiology · 2020
    Review
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  19. Thrombotic Regulation From the Endothelial Cell Perspectives.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Kefeng Zhai
Youmei Tang
Yuanyuan Zhang
Fang Li
Yan Wang
Zhengyu Cao
Jun YuDr. Jun Yu, Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT 06519, USA, Tel.: +1 203 7372869, Fax: +1 203 7372290, E-mail: jun.yu@yale.edu.
Junping KouDr. Junping Kou, State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, P. R. China, Tel./Fax: +86 25 86185158, E-mail: junpingkou@cpu.edu.cn.
Boyang Yu
Yale University · USChina Pharmaceutical University · CN

Funding

Role of RTN-4 in AtherosclerosisR56HL117064 · NHLBI · YALE UNIVERSITY · PI YU, JUN · 2013 to 2013
$416k
NHLBI NIH HHS R56 HL117064
6 · The paper itself

Abstract

Non-muscle myosin heavy chain IIA (NMMHC IIA) has been shown to be involved in thrombus formation and inflammatory microparticle release in endothelial cells. However, the role of NMMHC IIA in regulating the expression of tissue factor (TF) and deep venous thrombosis remains to be elucidated. In the present study, endothelial cells were stimulated with tumour necrosis factor-α (TNF-α) to induce TF expression. Pretreatment with the NMMHC II inhibitor blebbistatin suppressed the mRNA and protein expressions as well as the procoagulant activity of TF in a dose-dependent manner. Blebbistatin enhanced Akt and GSK3β phosphorylation and inhibited NF-κB p65 nuclear translocation and IκBα degradation. These observations were similar to the effect of CHIR99021, a GSK3β inhibitor. TF downregulation by blebbistatin was antagonised by the PI3K inhibitor, wortmannin. Furthermore, siRNA knockdown of NMMHC IIA, but not IIB or IIC, inhibited TF expression, activated Akt/GSK3β and suppressed NF-κB signalling pathways, whereas the overexpression of NMMHC IIA increased TF expression. The binding of NMMHC IIA and TNF receptor 2 mediated signal internalisation in TNF-α-stimulated endothelial cells. Importantly, blebbistatin decreased endothelium NMMHC IIA and TF expression, deactivated GSK3β by inducing its phosphorylation, suppressed p65 nuclear translocation, and inhibited thrombus formation in a mouse deep venous thrombosis model.Our findings provide solid evidence that inhibition of NMMHC II, most likely NMMHC IIA, impedes TF expression and venous thrombosis via Akt/GSK3β-NF-κB signalling pathways in the endothelium both in vitro and in vivo. NMMHC IIA might be a potential novel target for the treatment of thrombotic disorders.

Indexed as

Active Transport, Cell NucleusAnimalsDisease Models, AnimalDose-Response Relationship, DrugEndothelial CellsFibrinolytic AgentsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHEK293 CellsHeterocyclic Compounds, 4 or More RingsHumansI-kappa B ProteinsMice, Inbred C57BLMolecular Motor ProteinsMyosin Heavy ChainsNF-kappa BblebbistatinFibrinolytic AgentsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, mouseHeterocyclic Compounds, 4 or More RingsI-kappa B ProteinsMolecular Motor ProteinsMYH9 protein, humanMyh9 protein, mouseMyosin Heavy ChainsNF-kappa BNonmuscle Myosin Type IIAProtein Kinase InhibitorsProto-Oncogene Proteins c-aktReceptors, Tumor Necrosis Factor, Type IIRELA protein, humanThromboplastinTNFRSF1B protein, humanTranscription Factor RelATumor Necrosis Factor-alphaendotheliumNMMHC IIAsignalling transductiontissue factorvenous thrombosis

Identifiers

PMID25881103
PMCPMC5993197
OpenAlexW2088056870

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.