Evidence map›Paper›PMID 34205045›Full record

ArticleInternational journal of molecular sciences2021

Sodium Glucose Co-Transporter 2 Inhibitors Ameliorate Endothelium Barrier Dysfunction Induced by Cyclic Stretch through Inhibition of Reactive Oxygen Species.

Xiaoling Li, Gregor Römer, Raphaela P Kerindongo, Jeroen Hermanides, Martin Albrecht, Markus W Hollmann, Coert J Zuurbier, Benedikt Preckel, Nina C Weber

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
7.6field-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

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Review
  9. The endothelium response to kidney injury.Nature reviews. Nephrology · 2026
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Observational
  16. Review
  17. Potential protective role ofFrontiers in medicine · 2025
    Article
  18. Review
  19. Article
  20. Review
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

9 authors at 2 institutions in 2 countries.

Xiaoling LiLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Gregor RömerLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Raphaela P KerindongoLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Jeroen HermanidesLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0003-2239-1260
Martin AlbrechtDepartment of Anesthesiology and Intensive Care Medicine, Universitätsklinikum Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.ORCID 0000-0003-2580-768X
Markus W HollmannLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Coert J ZuurbierLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0001-8361-2448
Benedikt PreckelLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0003-4412-9183
Nina C WeberLaboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0003-1111-9042
Amsterdam University Medical Centers · NLUniversity Hospital Schleswig-Holstein · DE

Funding

Chinese Scholarship Council (CSC) 201906210054
6 · The paper itself

Abstract

SGLT-2i's exert direct anti-inflammatory and anti-oxidative effects on resting endothelial cells. However, endothelial cells are constantly exposed to mechanical forces such as cyclic stretch. Enhanced stretch increases the production of reactive oxygen species (ROS) and thereby impairs endothelial barrier function. We hypothesized that the SGLT-2i's empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) exert an anti-oxidative effect and alleviate cyclic stretch-induced endothelial permeability in human coronary artery endothelial cells (HCAECs). HCAECs were pre-incubated with one of the SGLT-2i's (1 µM EMPA, 1 µM DAPA and 3 µM CANA) for 2 h, followed by 10% stretch for 24 h. HCAECs exposed to 5% stretch were considered as control. Involvement of ROS was measured using N-acetyl-l-cysteine (NAC). The sodium-hydrogen exchanger 1 (NHE1) and NADPH oxidases (NOXs) were inhibited by cariporide, or GKT136901, respectively. Cell permeability and ROS were investigated by fluorescence intensity imaging. Cell permeability and ROS production were increased by 10% stretch; EMPA, DAPA and CANA decreased this effect significantly. Cariporide and GKT136901 inhibited stretch-induced ROS production but neither of them further reduced ROS production when combined with EMPA. SGLT-2i's improve the barrier dysfunction of HCAECs under enhanced stretch and this effect might be mediated through scavenging of ROS. Anti-oxidative effect of SGLT-2i's might be partially mediated by inhibition of NHE1 and NOXs.

Indexed as

Benzhydryl CompoundsCanagliflozinCell Membrane PermeabilityEndothelial CellsGlucosidesGuanidinesHumansInflammationNADPH OxidasesOxidative StressPyrazolesPyridonesReactive Oxygen SpeciesSodium-Glucose Transporter 2 InhibitorsSodium-Glucose Transport ProteinsSodium-Hydrogen Exchanger 12-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo(4,3-c)pyridine-3,6(2H,5H)-dioneBenzhydryl CompoundsCanagliflozincariporidedapagliflozinempagliflozinGlucosidesGuanidinesNADPH OxidasesPyrazolesPyridonesReactive Oxygen SpeciesSLC9A1 protein, humanSodium-Glucose Transporter 2 InhibitorsSodium-Glucose Transport ProteinsSodium-Hydrogen Exchanger 1Sulfonescell permeabilityNADPH oxidases (NOXs)reactive oxygen species (ROS)sodium glucose co-transporter 2 inhibitors (SGLT-2i’s)sodium-hydrogen exchanger 1 (NHE1)

Identifiers

PMID34205045
PMCPMC8199893
OpenAlexW3170013427

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.