Evidence map›Paper›PMID 33340902›Full record

ArticleRedox biology2021

Glycocalyx sialic acids regulate Nrf2-mediated signaling by fluid shear stress in human endothelial cells.

Paraskevi-Maria Psefteli, Phoebe Kitscha, Gema Vizcay, Roland Fleck, Sarah J Chapple, Giovanni E Mann, Mark Fowler, Richard C Siow

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
6.1field-weighted citation impact, top 2% 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

37 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Integrating molecular and cellular components of endothelial shear stress mechanotransduction.American journal of physiology. Heart and circulatory physiology · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Is fluid retention a cardiovascular risk factor?Clinical hemorheology and microcirculation · 2024
    Review
  17. Review
  18. Review
  19. Response of cells and tissues to shear stress.Journal of cell science · 2023
    Review
  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

8 authors at 2 institutions in 1 country.

Paraskevi-Maria PsefteliKing's British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
Phoebe KitschaKing's British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
Gema VizcayCentre for Ultrastructural Imaging, Faculty of Life Sciences & Medicine, King's College London, London, SE1 1UL, United Kingdom.
Roland FleckCentre for Ultrastructural Imaging, Faculty of Life Sciences & Medicine, King's College London, London, SE1 1UL, United Kingdom.
Sarah J ChappleKing's British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
Giovanni E MannKing's British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom.
Mark FowlerStrategic Science Group, Unilever R&D, Colworth Science Park, Bedford, MK44 1LQ, United Kingdom.
Richard C SiowKing's British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9NH, United Kingdom. Electronic address: richard.siow@kcl.ac.uk.
King's College London · GBUnilever (United Kingdom) · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M502741/1British Heart Foundation FS/13/55/30643
6 · The paper itself

Abstract

Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is critical for vascular endothelial redox homeostasis in regions of high, unidirectional shear stress (USS), however the underlying mechanosensitive mediators are not fully understood. The endothelial glycocalyx is disrupted in arterial areas exposed to disturbed blood flow that also exhibit enhanced oxidative stress leading to atherogenesis. We investigated the contribution of glycocalyx sialic acids (SIA) to Nrf2 signaling in human endothelial cells (EC) exposed to atheroprotective USS or atherogenic low oscillatory shear stress (OSS). Cells exposed to USS exhibited a thicker glycocalyx and enhanced turnover of SIA which was reduced in cells cultured under OSS. Physiological USS, but not disturbed OSS, enhanced Nrf2-mediated expression of antioxidant enzymes, which was attenuated following SIA cleavage with exogenous neuraminidase. SIA removal disrupted kinase signaling involved in the nuclear accumulation of Nrf2 elicited by USS and promoted mitochondrial reactive oxygen species accumulation. Notably, knockdown of the endogenous sialidase NEU1 potentiated Nrf2 target gene expression, directly implicating SIA in regulation of Nrf2 signaling by USS. In the absence of SIA, deficits in Nrf2 responses to physiological flow were also associated with a pro-inflammatory EC phenotype. This study demonstrates that the glycocalyx modulates endothelial redox state in response to shear stress and provides the first evidence of an atheroprotective synergism between SIA and Nrf2 antioxidant signaling. The endothelial glycocalyx therefore represents a potential therapeutic target against EC dysfunction in cardiovascular disease and redox dyshomeostasis in ageing.

Indexed as

Endothelial CellsNF-E2-Related Factor 2GlycocalyxHeme Oxygenase-1HumansOxidative StressSialic AcidsStress, MechanicalHeme Oxygenase-1NFE2L2 protein, humanNF-E2-Related Factor 2Sialic AcidsEndothelial glycocalyxGlutamate-cysteine ligaseHeme oxygenase-1Hemodynamic shear stressMechanotransductionNAD(P)H quinone oxidoreductase-1NeuraminidaseNrf2Sialic acid

Identifiers

PMID33340902
PMCPMC7750408
OpenAlexW3109949435

What OpenQuestion holds

Textmetadata
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.