Differential roles of eNOS in late effects of VEGF-A on hyperpermeability in different types of endothelial cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 Dec 2023
05 Dec 2023
Historique:
received:
03
03
2023
accepted:
06
11
2023
medline:
7
12
2023
pubmed:
6
12
2023
entrez:
5
12
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38052807
doi: 10.1038/s41598-023-46893-4
pii: 10.1038/s41598-023-46893-4
pmc: PMC10698188
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Nitric Oxide Synthase Type III
EC 1.14.13.39
Dextrans
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21436Subventions
Organisme : Slovenian Research Agency
ID : PI-0245
Organisme : Slovenian Research Agency
ID : J3-2526
Organisme : EFSD/Boehringer Ingelheim European Research Programme in Microvascular Complications of Diabetes
ID : BI18_4
Informations de copyright
© 2023. The Author(s).
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