Evidence mapPaperPMID 35325071Full record

ArticleCardiovascular research2022

Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction.

Junchul Shin, Svyatoslav Tkachenko, Malay Chaklader, Connor Pletz, Kanwardeep Singh, Gamze B Bulut, Young Min Han, Kelly Mitchell, Richard A Baylis, Andrey A Kuzmin and 7 more

Open access · greenAbstract read
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-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

18 citing papers in PubMed, 31 citations in OpenAlex.

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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 4 institutions in 2 countries.

Junchul ShinDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0002-4959-6680
Svyatoslav TkachenkoDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Malay ChakladerDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Connor PletzDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Kanwardeep SinghDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Gamze B BulutRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Young Min HanCenter for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, USA.
Kelly MitchellDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Richard A BaylisRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Andrey A KuzminRussian Academy of Sciences, Institute of Cytology, St Petersburg, Russian Federation.
Bo HuDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Justin D LathiaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Olga Stenina-AdognraviDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Eugene PodrezDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Tatiana V ByzovaDepartment of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Gary K OwensRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Olga A CherepanovaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0003-0045-8102
Cleveland Clinic Lerner College of Medicine · USUniversity of Virginia · USGeorgia State University · USInstitute of Cytology · RU

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · 1985 to 2025
$5.4M
Activation of integrin on blood &endothelial cellsR01HL071625 · CLEVELAND CLINIC LERNER COL/MED-CWRU · 2003 to 2005
$1.0M
NHLBI NIH HHS R01 HL071625NHLBI NIH HHS R01 HL087867NHLBI NIH HHS R01 HL098538NHLBI NIH HHS R01 HL136314NHLBI NIH HHS R01 HL145536NHLBI NIH HHS R01 HL155165NHLBI NIH HHS R56 HL148025NHLBI NIH HHS T32 HL007284
6 · The paper itself

Abstract

aimsUntil recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis. METHODS AND

resultsSpecifically, we show that EC-specific Oct4 knockout resulted in increased lipid, LGALS3+ cell accumulation, and altered plaque characteristics consistent with decreased plaque stability. A combination of single-cell RNA sequencing and EC-lineage-tracing studies revealed increased EC activation, endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction in the absence of OCT4. Furthermore, we show that the adenosine triphosphate (ATP) transporter, ATP-binding cassette (ABC) transporter G2 (ABCG2), is a direct target of OCT4 in EC and establish for the first time that the OCT4/ABCG2 axis maintains EC metabolic homeostasis by regulating intracellular heme accumulation and related reactive oxygen species production, which, in turn, contributes to atherogenesis.

conclusionsThese results provide the first direct evidence that OCT4 has a protective metabolic function in EC and identifies vascular OCT4 and its signalling axis as a potential target for novel therapeutics.

Indexed as

AtherosclerosisPlaque, AtheroscleroticCell LineageHumansMyocytes, Smooth MuscleSignal TransductionABCG2AtherosclerosisHemeOCT4ROS

Identifiers

PMID35325071
PMCPMC9890633
OpenAlexW4221072165

What Socratic holds

Textmetadata
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 Socratic graph.