Evidence map›Paper›PMID 23480518›Full record

ArticleJournal of thrombosis and haemostasis : JTH2013

Comparison of the inhibitory activities of human tissue factor pathway inhibitor (TFPI)α and TFPIβ.

S A Maroney, P E Ellery, J P Wood, J P Ferrel, N D Martinez, A E Mast

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Intersection of regulatory pathways controlling hemostasis and hemochorial placentation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  7. The contribution of TFPIα to the hemostatic response to injury in mice.Journal of thrombosis and haemostasis : JTH · 2021
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Defective fibrin deposition and thrombus stability in BambiJournal of thrombosis and haemostasis : JTH · 2019
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Targeting TFPI for hemophilia treatment.Thrombosis research · 2016
    Review
  19. Review
  20. Article
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

6 authors at 2 institutions in 1 country.

S A MaroneyBlood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA.
P E Ellery
J P Wood
J P Ferrel
N D Martinez
A E Mast
Versiti Blood Center of Wisconsin · USMedical College of Wisconsin · US

Funding

Clincal and Translational Science AwardUL1TR000055 · NCATS · MEDICAL COLLEGE OF WISCONSIN · PI SHAKER, REZA NONE · 2012 to 2015
$11.3M
Tissue Factor Pathway Inhibitor Binding Proteins on EndoR01HL068835 · NHLBI · VERSITI WISCONSIN, INC. · PI Alan E Mast · 2002 to 2026
$9.7M
Cysteine oxidation in the heartR01HL091469 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI Junichi Sadoshima · 2008 to 2026
$9.4M
RESEARCH TRAINING IN TRANSFUSION SCIENCET32HL007209 · NHLBI · VERSITI WISCONSIN, INC. · PI WHITE, II, GILBERT C. · 1985 to 2019
$2.9M
The Biochemistry and Physiology of Platelet TFPIK01HL096419 · NHLBI · VERSITI WISCONSIN, INC. · PI MARONEY, SUSAN ANTONE · 2009 to 2013
$626k
NCATS NIH HHS UL1 TR000055NHLBI NIH HHS HL007209NHLBI NIH HHS HL068835NHLBI NIH HHS HL091469NHLBI NIH HHS K01 HL096419NHLBI NIH HHS R01 HL068835NHLBI NIH HHS R01 HL091469NHLBI NIH HHS T32 HL007209
6 · The paper itself

Abstract

backgroundTissue factor pathway inhibitor (TFPI) is an alternatively spliced protein with two isoforms, TFPIα and TFPIβ, which differ in their C-terminal structure and cellular localization. Detailed characterization of their inhibitory activity is needed to define potentially unique inhibitory roles in tissue factor (TF)-mediated thrombotic and inflammatory disease, and to understand how pharmaceuticals targeted to different structural regions of the TFPI isoforms alter hemostasis in hemophilia patients.

methodsThe TF inhibitory activity of TFPIβ localized to the surface of CHO cells was compared with that of soluble TFPIα by the use of in vitro and in vivo assays.

resultsIn TF-factor VIIa-mediated FXa generation assays, TFPIβ was a slightly better inhibitor than TFPIα, which was approximately three-fold better than TFPI-160, a soluble, altered form of TFPI similar to TFPIβ. In direct FXa inhibitory assays, TFPIβ had an IC50 2.5-fold lower than that of TFPIα and 56-fold lower than that of TFPI-160. TFPIβ inhibited TF-mediated CHO cell migration though Matrigel, whereas TFPIα and TFPI-160 were poor inhibitors, demonstrating that TFPIβ effectively blocks TF-initiated signaling events during cellular migration through matrices that are not permeable to soluble forms of TFPI. Furthermore, TFPIβ inhibited TF-dependent CHO cell infiltration into lung tissue following tail vein injection into SCID mice, and blocked the development of consumptive coagulopathy.

conclusionsTFPIβ is a slightly better inhibitor of TF procoagulant activity than TFPIα. As a surface-associated protein, TFPIβ is a much better inhibitor of TF-mediated cellular migration than soluble TFPIα, and may specifically act in the inhibition of TF-mediated signaling events on inflamed endothelium and/or monocytes.

Indexed as

AnimalsCHO CellsCricetinaeCricetulusEnzyme-Linked Immunosorbent AssayHumansLipoproteinslipoprotein-associated coagulation inhibitorLipoproteins

Identifiers

PMID23480518
PMCPMC3656975
OpenAlexW1998611693

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.