Evidence map›Paper›PMID 32404004›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2020

PKC (Protein Kinase C)-δ Modulates AT (Antithrombin) Signaling in Vascular Endothelial Cells.

Sumith R Panicker, Indranil Biswas, Hemant Giri, Xiaofeng Cai, Alireza R Rezaie

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Thrombomodulin Regulates PTEN/AKT Signaling Axis in Endothelial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Article
  9. PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023
    Review
  10. Article
  11. Article
  12. Extracellular Histones Bind Vascular Glycosaminoglycans and Inhibit the Anti-Inflammatory Function of Antithrombin.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021
    Article
  13. Anticoagulant and signaling functions of antithrombin.Journal of thrombosis and haemostasis : JTH · 2020
    Review
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

5 authors at 1 institution in 1 country.

Sumith R PanickerFrom the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (S.R.P., I.B., H.G., X.C., A.R.R.).
Indranil BiswasFrom the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (S.R.P., I.B., H.G., X.C., A.R.R.).
Hemant GiriFrom the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (S.R.P., I.B., H.G., X.C., A.R.R.).
Xiaofeng CaiFrom the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (S.R.P., I.B., H.G., X.C., A.R.R.).
Alireza R RezaieFrom the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (S.R.P., I.B., H.G., X.C., A.R.R.).
Oklahoma Medical Research Foundation · US

Funding

Protease Activated Receptor Signaling by Coagulation ProteasesR01HL101917 · NHLBI · SAINT LOUIS UNIVERSITY · PI Lijun Xia · 2010 to 2026
$6.6M
Serpin Regulation of Coagulation ProteasesR01HL062565 · NHLBI · SAINT LOUIS UNIVERSITY · PI REZAIE, ALIREZA R. · 1999 to 2020
$6.2M
NHLBI NIH HHS R01 HL062565NHLBI NIH HHS R01 HL101917
6 · The paper itself

Abstract

objectiveNative and latent conformers of AT (antithrombin) induce anti-inflammatory and proapoptotic signaling activities, respectively, in vascular endothelial cells by unknown mechanisms. Synd-4 (syndecan-4) has been identified as a receptor that is involved in transmitting signaling activities of AT in endothelial cells. Approach and Results: In this study, we used flow cytometry, signaling assays, immunoblotting and confocal immunofluorescence microscopy to investigate the mechanism of the paradoxical signaling activities of high-affinity heparin (native) and low-affinity heparin (latent) conformers of AT in endothelial cells. We discovered that native AT binds to glycosaminoglycans on vascular endothelial cells via its heparin-binding D-helix to induce anti-inflammatory signaling responses by recruiting PKC (protein kinase C)-δ to the plasma membrane and promoting phosphorylation of the Synd-4 cytoplasmic domain at Ser179. By contrast, the binding of latent AT to endothelial cells to a site(s), which is not competed by the native AT, induces a proapoptotic effect by localizing PKC-δ to the perinuclear/nuclear compartment in endothelial cells. Overexpression of a dominant-negative form of PKC-δ resulted in inhibition of anti-inflammatory and proapoptotic signaling activities of both native and latent AT.

conclusionsThese results indicate that the native and latent conformers of AT may exert their distinct intracellular signaling effects through differentially modulating the subcellular localization of PKC-δ in endothelial cells.

Indexed as

6-Ketoprostaglandin F1 alphaActive Transport, Cell NucleusAnti-Inflammatory AgentsAntithrombin ProteinsApoptosisCell LineEndothelial CellsHeparan Sulfate ProteoglycansHumansIntercellular Adhesion Molecule-1PhosphorylationProtein BindingProtein Interaction Domains and MotifsProtein Kinase C-deltaSignal TransductionSyndecan-46-Ketoprostaglandin F1 alphaAnti-Inflammatory AgentsAntithrombin ProteinsHeparan Sulfate ProteoglycansICAM1 protein, humanIntercellular Adhesion Molecule-1PRKCD protein, humanProtein Kinase C-deltaSDC4 protein, humanSyndecan-4Vascular Cell Adhesion Molecule-1antithrombinendothelial cellsglycosaminoglycansheparinsyndecan-4

Identifiers

PMID32404004
PMCPMC7316612
OpenAlexW3024057397

What OpenQuestion holds

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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.