Evidence map›Paper›PMID 27183216›Full record

ArticleNature medicine2016

Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective.

Olga A Cherepanova, Delphine Gomez, Laura S Shankman, Pamela Swiatlowska, Jason Williams, Olga F Sarmento, Gabriel F Alencar, Daniel L Hess, Melissa H Bevard, Elizabeth S Greene and 7 more

Abstract read
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed, 1 pooled it
10.1field-weighted citation impact, top 1% 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

148 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.

  1. Pooled it
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  17. Kindlin-2 Deletion in Mural Cells Leads to Vascular Instability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
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88 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 3 countries.

Olga A CherepanovaRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Delphine GomezRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Laura S ShankmanRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Pamela SwiatlowskaRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Jason WilliamsThe Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas Houston Medical School, Houston, Texas, USA.
Olga F SarmentoDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Gabriel F AlencarRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Daniel L HessRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Melissa H BevardRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Elizabeth S GreeneRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Meera MurgaiRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Stephen D TurnerBioinformatics Core, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Yong-Jian GengThe Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas Houston Medical School, Houston, Texas, USA.
Stefan BekiranovDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.
Jessica J ConnellyRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Alexey TomilinInstitute of Cytology, Russian Academy of Science, Saint Petersburg, Russia.
Gary K OwensRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
University of Virginia · USThe University of Texas Health Science Center at Houston · USInstitute of Cytology · RUMayo Clinic in Arizona · USUniversity of Gdańsk · PL

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007267 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GARCIA-BLANCO, MARIANO A. · 1985 to 2024
$13.4M
MOLECULAR REGULATION OF SMOOTH MUSCLE DIFFERENTIATIONR01HL038854 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI OWENS, GARY K · 1987 to 2010
$3.7M
Role of OxPLs and Oct4 in SMC Phenotypic Switching in AtherosclerosisR01HL087867 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2008 to 2016
$3.5M
Epigenetic Control of Smooth Muscle Cell Lineage and Phenotypic SwitchingR01HL057353 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2008 to 2016
$3.5M
KLF4-Dependent Regulation of SMC Differentiation and Phenotypic SwitchingR01HL098538 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2010 to 2013
$2.7M
Role of IL1b in Regulating SMC and Macrophage Differentiation in AtherosclerosisR01HL121008 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2014 to 2017
$2.2M
Epigenomics of AtherosclerosisR01HL100257 · NHLBI · UNIVERSITY OF VIRGINIA · PI CONNELLY, JESSICA J · 2009 to 2012
$1.5M
Molecular Dissection of Cardiovascular Disease: From Genes to Models to FunctionR00HL089412 · NHLBI · UNIVERSITY OF VIRGINIA · PI CONNELLY, JESSICA J · 2009 to 2011
$747k
American Heart Association-American Stroke Association 11PRE7750030American Heart Association-American Stroke Association 13POST17080043NHLBI NIH HHS R00 HL089412NHLBI NIH HHS R01 HL038854NHLBI NIH HHS R01 HL057353NHLBI NIH HHS R01 HL087867NHLBI NIH HHS R01 HL098538NHLBI NIH HHS R01 HL100257NHLBI NIH HHS R01 HL121008NHLBI NIH HHS T32 HL007284
6 · The paper itself

Abstract

Although somatic cell activation of the embryonic stem cell (ESC) pluripotency factor OCT4 has been reported, this previous work has been controversial and has not demonstrated a functional role for OCT4 in somatic cells. Here we demonstrate that smooth muscle cell (SMC)-specific conditional knockout of Oct4 in Apoe(-/-) mice resulted in increased lesion size and changes in lesion composition that are consistent with decreased plaque stability, including a thinner fibrous cap, increased necrotic core area, and increased intraplaque hemorrhage. Results of SMC-lineage-tracing studies showed that these effects were probably the result of marked reductions in SMC numbers within lesions and SMC investment within the fibrous cap, which may result from impaired SMC migration. The reactivation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was hypoxia inducible factor-1α (HIF-1α, encoded by HIF1A) and Krüppel-like factor-4 (KLF4)-dependent. These results provide the first direct evidence that OCT4 has a functional role in somatic cells, and they highlight the potential role of OCT4 in normal and diseased somatic cells.

Indexed as

AnimalsAortaApolipoproteins EAtherosclerosisBlotting, WesternCell LineageCell MovementCell SurvivalChromatin ImmunoprecipitationCoronary Artery DiseaseDiet, WesternHumansHypoxia-Inducible Factor 1, alpha SubunitKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleApolipoproteins EHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsOctamer Transcription Factor-3POU5F1 protein, humanPou5f1 protein, mouse

Identifiers

PMID27183216
PMCPMC4899256
OpenAlexW2400111296

What OpenQuestion holds

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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.