Evidence map›Paper›PMID 25147340›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Canonical Wnt signaling induces vascular endothelial dysfunction via p66Shc-regulated reactive oxygen species.

Ajit Vikram, Young-Rae Kim, Santosh Kumar, Asma Naqvi, Timothy A Hoffman, Ajay Kumar, Francis J Miller, Cuk-Seong Kim, Kaikobad Irani

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

42 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. The Role of Sclerostin in Bone and Ectopic Calcification.International journal of molecular sciences · 2020
    Review
  17. A Positive Feed Forward Loop between Wnt/Oxidative medicine and cellular longevity · 2020
    Article
  18. The Role of Wnt/β-Catenin Pathway Mediators in Aortic Valve Stenosis.Frontiers in cell and developmental biology · 2020
    Article
  19. Article
  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

9 authors at 2 institutions in 1 country.

Ajit VikramFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.). ajit-vikram@uiowa.edu kaikobad-irani@uiowa.edu.
Young-Rae KimFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Santosh KumarFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Asma NaqviFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Timothy A HoffmanFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Ajay KumarFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Francis J MillerFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Cuk-Seong KimFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.).
Kaikobad IraniFrom the Cardiovascular Division, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City (A.V., Y.-R.K., S.K., F.J.M., K.I.); Cardiovascular Institute, University of Pittsburgh, PA (A.N., A.K.); Department of Biochemistry and Molecular Biology, University of Louisville, KY (T.A.H.); and Department of Physiology, Chungnam National University, Daejeon, Korea (C.-S.K.). ajit-vikram@uiowa.edu kaikobad-irani@uiowa.edu.
University of Pittsburgh · USUniversity of Louisville · US

Funding

Redox-and acetylation-dependent control of vascular toneR01HL070929 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI IRANI, KAIKOBAD J. · 2002 to 2011
$3.3M
Transcriptional and Epigenetic regulation of P66shc: relevance to endothelial funR01HL094959 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI IRANI, KAIKOBAD J. · 2009 to 2010
$758k
Aspirin-induced, HDAC-modulated, regulation of endothelial function and vascularR21HL098892 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI IRANI, KAIKOBAD J. · 2011 to 2012
$417k
NHLBI NIH HHS R01 HL070929NHLBI NIH HHS R01 HL094959NHLBI NIH HHS R21 HL098892
6 · The paper itself

Abstract

objectiveReactive oxygen species regulate canonical Wnt signaling. However, the role of the redox regulatory protein p66(Shc) in the canonical Wnt pathway is not known. We investigated whether p66(Shc) is essential for canonical Wnt signaling in the endothelium and determined whether the canonical Wnt pathway induces vascular endothelial dysfunction via p66(Shc)-mediated oxidative stress. APPROACH AND

resultsThe canonical Wnt ligand Wnt3a induced phosphorylation (activation) of p66(Shc) in endothelial cells. Wnt3a-stimulated dephosphorylation of β-catenin, and β-catenin-dependent transcription, was inhibited by knockdown of p66(Shc). Exogenous H2O2-induced β-catenin dephosphorylation was also mediated by p66(Shc). Moreover, p66(Shc) overexpression dephosphorylated β-catenin and increased β-catenin-dependent transcription, independent of Wnt3a ligand. P66(Shc)-induced β-catenin dephosphorylation was inhibited by antioxidants N-acetyl cysteine and catalase. Wnt3a upregulated endothelial NADPH oxidase-4, and β-catenin dephosphorylation was suppressed by knocking down NADPH oxidase-4 and by antioxidants. Wnt3a increased H2O2 levels in endothelial cells and impaired endothelium-dependent vasorelaxation in mouse aortas, both of which were rescued by p66(Shc) knockdown. P66(Shc) knockdown also inhibited adhesion of monocytes to Wnt3a-stimulated endothelial cells. Furthermore, constitutively active β-catenin expression in the endothelium increased vascular reactive oxygen species and impaired endothelium-dependent vasorelaxation. In vivo, high-fat diet feeding-induced endothelial dysfunction in mice was associated with increased endothelial Wnt3a, dephosphorylated β-catenin, and phosphorylated p66(Shc). High-fat diet-induced dephosphorylation of endothelial β-catenin was diminished in mice in which p66(Shc) was knocked down.

conclusionsp66(Shc) plays a vital part in canonical Wnt signaling in the endothelium and mediates Wnt3a-stimulated endothelial oxidative stress and dysfunction.

Indexed as

Oxidative StressWnt Signaling PathwayAnimalsAortabeta CateninCattleCoculture TechniquesDiet, High-FatDisease Models, AnimalEndothelial CellsHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsHyperlipidemiasMiceMice, Inbred C57BLbeta CateninCTNNB1 protein, humanCTNNB1 protein, mouseNADPH OxidasesReactive Oxygen SpeciesSHC1 protein, humanShc1 protein, mouseShc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Vasodilator AgentsWnt3A ProteinWNT3A protein, humanWnt3a protein, mouseendothelial cellsoxidation–reductionp66Shc proteinreactive oxygen speciesWnt signaling pathway

Identifiers

PMID25147340
PMCPMC6069972
OpenAlexW2101314557

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.