Evidence map›Paper›PMID 23619421›Full record

ReviewCardiovascular research2013

The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo.

Peter F Davies, Mete Civelek, Yun Fang, Ingrid Fleming

Open access · bronzeAbstract readReview
In one paragraph

Review in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.

0numbers the graph read from it
0cells of the map it votes in
176citing papers in PubMed
12.1field-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

176 citing papers in PubMed, 321 citations in OpenAlex.

  1. Trial
  2. Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
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  8. Purine metabolic adaptation protects the endothelium from disturbed flow-induced DNA damage and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Biomechanics of Plaque Rupture and Cardiovascular Calcification.Advances in experimental medicine and biology · 2026
    Review
  10. Review
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  12. Article
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  14. Review
  15. Review
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  19. Review
  20. Article

116 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

4 authors at 2 institutions in 2 countries.

Peter F DaviesInstitute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA. pfd@mail.med.upenn.edu
Mete Civelek
Yun Fang
Ingrid Fleming
University of Pennsylvania · USGoethe University Frankfurt · DE

Funding

STUDIES OF PLATELET ADHERENCE TO OSTEOPONTINP01HL062250 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 1999 to 2013
$28.4M
Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
miR-10a regulation of regional arterial endothelial phenotypes in atherosclerosisK99HL103789 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI FANG, YUN · 2011 to 2012
$172k
NHLBI NIH HHS K99 HL103789NHLBI NIH HHS P01HL062250NHLBI NIH HHS T32 HL069766NHLBI NIH HHS T32HL07954NHLBI NIH HHS T32HL69766
6 · The paper itself

Abstract

Atherosclerosis initiates at predictable focal sites and develops to a spatially regional disease with limited distribution. There is compelling evidence that links haemodynamics to the localized origin of atherosclerotic lesions. Arterial flow in vivo is unsteady, dynamically complex, and regionally variable. Sites susceptible to atherosclerosis near arterial branches and curves are associated with regions of disturbed blood flow that contain repetitive phases of flow reversal resulting in steep multidirectional temporal and spatial gradients of wall shear stresses. Endothelium in atherosusceptible regions relative to protected sites shows activation of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), the altered expression of pro-inflammatory Nuclear Factor kappa B (NFκB) and oxidant/antioxidant pathways, and low expression of major protective factors, notably endothelial nitric oxide synthase and Kruppel-like Factors KLF2 and KLF4. At some atherosusceptible locations, reactive oxygen species levels are significantly elevated. Here we describe flow-related phenotypes identified in steady-state in vivo and outline some of the molecular mechanisms that may contribute to pre-lesional atherosusceptibility as deduced from complementary cell experiments in vitro. We conclude that disturbed flow is a significant local risk factor for atherosclerosis that induces a chronic low-level inflammatory state, an adaptive response to ensure continued function at the expense of increased susceptibility to atherogenesis. Surprisingly, when challenged by short-term hypercholesterolaemia in vivo, atherosusceptible endothelial phenotype was resistant to greater pro-inflammatory expression, suggesting that sustained hyperlipidaemia is required to overcome these protective characteristics.

Indexed as

HemodynamicsMechanotransduction, CellularAnimalsAtherosclerosisBiomechanical PhenomenaEndothelial CellsEndothelium, VascularHumansHypercholesterolemiaInflammationKruppel-Like Factor 4PhenotypeRegional Blood FlowStress, MechanicalKruppel-Like Factor 4AtherosclerosisEndothelial phenotypeGenomicsvHaemodynamicsInflammation

Identifiers

PMID23619421
PMCPMC3695748
OpenAlexW2003213503

What OpenQuestion 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 OpenQuestion graph.