Evidence map›Paper›PMID 38052807›Full record

ArticleScientific reports2023

Differential roles of eNOS in late effects of VEGF-A on hyperpermeability in different types of endothelial cells.

Esmeralda K Bosma, Shahan Darwesh, Yasmin I Habani, Maxime Cammeraat, Paola Serrano Martinez, Mathilda E van Breest Smallenburg, Jia Y Zheng, Ilse M C Vogels, Cornelis J F van Noorden, Reinier O Schlingemann and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Faricimab Reverts VEGF-AInternational journal of molecular sciences · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. 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

11 authors at 4 institutions in 3 countries.

Esmeralda K BosmaOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Shahan DarweshOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Yasmin I HabaniOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Maxime CammeraatOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Paola Serrano MartinezOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Mathilda E van Breest SmallenburgOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Jia Y ZhengOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Ilse M C VogelsOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Cornelis J F van NoordenOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Reinier O SchlingemannOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Ingeborg KlaassenOcular Angiogenesis Group, Department of Ophthalmology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. i.klaassen@amsterdamumc.nl.ORCID 0000-0003-1695-9403
Amsterdam Neuroscience · NLAmsterdam University Medical Centers · NLHôpital Ophtalmique Jules-Gonin · CHNational Institute of Biology · SI

Funding

EFSD/Boehringer Ingelheim European Research Programme in Microvascular Complications of Diabetes BI18_4Slovenian Research Agency J3-2526Slovenian Research Agency PI-0245
6 · The paper itself

Abstract

Vascular endothelial growth factor (VEGF)-A induces endothelial hyperpermeability, but the molecular pathways remain incompletely understood. Endothelial nitric oxide synthase (eNOS) regulates acute effects of VEGF-A on permeability of endothelial cells (ECs), but it remains unknown whether and how eNOS regulates late effects of VEGF-A-induced hyperpermeability. Here we show that VEGF-A induces hyperpermeability via eNOS-dependent and eNOS-independent mechanisms at 2 days after VEGF-A stimulation. Silencing of expression of the eNOS gene (NOS3) reduced VEGF-A-induced permeability for dextran (70 kDa) and 766 Da-tracer in human dermal microvascular ECs (HDMVECs), but not in human retinal microvascular ECs (HRECs) and human umbilical vein ECs (HUVECs). However, silencing of NOS3 expression in HRECs increased permeability to dextran, BSA and 766 Da-tracer in the absence of VEGF-A stimulation, suggesting a barrier-protective function of eNOS. We also investigated how silencing of NOS3 expression regulates the expression of permeability-related transcripts, and found that NOS3 silencing downregulates the expression of PLVAP, a molecule associated with trans-endothelial transport via caveolae, in HDMVECs and HUVECs, but not in HRECs. Our findings underscore the complexity of VEGF-A-induced permeability pathways in ECs and the role of eNOS therein, and demonstrate that different pathways are activated depending on the EC phenotype.

Indexed as

Nitric Oxide Synthase Type IIIVascular Endothelial Growth Factor ACaveolaeCells, CulturedDextransHumansHuman Umbilical Vein Endothelial CellsDextransNitric Oxide Synthase Type IIINOS3 protein, humanVascular Endothelial Growth Factor A

Identifiers

PMID38052807
PMCPMC10698188
OpenAlexW4389338767

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.