Evidence map›Paper›PMID 34470477›Full record

ReviewArteriosclerosis, thrombosis, and vascular biology2021

Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4).

Carmen Yap, Arnout Mieremet, Carlie J M de Vries, Dimitra Micha, Vivian de Waard

Open access · hybridAbstract readReview
In one paragraph

Review in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed
14.8field-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

181 citing papers in PubMed, 265 citations in OpenAlex.

  1. Article
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  7. ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  8. Review
  9. LINC00152/miR-145-5p/KLF4 ceRNA Axis: Diagnostic and Prognostic Value in Aortic Dissection.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2026
    Article
  10. Article
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  12. PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
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121 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

5 authors at 2 institutions in 1 country.

Carmen Yap *Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Location Academic Medical Center, The Netherlands (C.Y., A.M., C.J.M.d.V., V.d.W.).ORCID 0000-0001-5272-0753
Arnout Mieremet *Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Location Academic Medical Center, The Netherlands (C.Y., A.M., C.J.M.d.V., V.d.W.).ORCID 0000-0002-8330-7491
Carlie J M de VriesDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Location Academic Medical Center, The Netherlands (C.Y., A.M., C.J.M.d.V., V.d.W.).
Dimitra MichaDepartment of Clinical Genetics, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam, Amsterdam UMC, Location VU University Medical Center, Amsterdam, The Netherlands (D.M.).ORCID 0000-0001-7890-4411
Vivian de WaardDepartment of Medical Biochemistry, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam UMC, Location Academic Medical Center, The Netherlands (C.Y., A.M., C.J.M.d.V., V.d.W.).
Amsterdam University Medical Centers · NLAmsterdam Neuroscience · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple layers of vascular smooth muscle cells (vSMCs) are present in blood vessels forming the media of the vessel wall. vSMCs provide a vessel wall structure, enabling it to contract and relax, thus modulating blood flow. They also play a crucial role in the development of vascular diseases, such as atherosclerosis and aortic aneurysm formation. vSMCs display a remarkable high degree of plasticity. At present, the number of different vSMC phenotypes has only partially been characterized. By mapping vSMC phenotypes in detail and identifying triggers for phenotype switching, the relevance of the different phenotypes in vascular disease may be identified. Up until recently, vSMCs were classified as either contractile or dedifferentiated (ie, synthetic). However, single-cell RNA sequencing studies revealed such dedifferentiated arterial vSMCs to be highly diverse. Currently, no consensus exist about the number of vSMC phenotypes. Therefore, we reviewed the data from relevant single-cell RNA sequencing studies, and classified a total of 6 vSMC phenotypes. The central dedifferentiated vSMC type that we classified is the mesenchymal-like phenotype. Mesenchymal-like vSMCs subsequently seem to differentiate into fibroblast-like, macrophage-like, osteogenic-like, and adipocyte-like vSMCs, which contribute differentially to vascular disease. This phenotype switching between vSMCs requires the transcription factor KLF4 (Kruppel-like factor 4). Here, we performed an integrated analysis of the data about the recently identified vSMC phenotypes, their associated gene expression profiles, and previous vSMC knowledge to better understand the role of vSMC phenotype transitions in vascular pathology.

Indexed as

Cell DifferentiationCell PlasticityAnimalsAtherosclerosisCell ProliferationHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMuscle, Smooth, VascularMyocytes, Smooth MusclePhenotypePlaque, AtheroscleroticSignal TransductionKLF4 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription Factorsatherosclerosiscardiovascular diseasemyocytesphenotypesmooth muscle

Identifiers

PMID34470477
PMCPMC8545254
OpenAlexW3198290615

What OpenQuestion holds

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LicenceCC BY
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.