| Title: | Diferential roles of eNOS in late efects ofVEGF‑A on hyperpermeability in diferent types of endothelial cells |
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| Authors: | ID Bosma, Esmeralda K. (Author)
ID Darwesh, Shahan (Author)
ID Habani, Yasmin I. (Author)
ID Cammeraat, Maxime (Author)
ID Serrano Martinez, Paola (Author)
ID Breest Smallenburg, Mathilda E. van (Author)
ID Zheng, JiaY. (Author)
ID Vogels, Ilse M.C. (Author)
ID Noorden, Cornelis J. F. van (Author)
ID Schlingemann, Reinier O. (Author)
ID Klaassen, Ingeborg (Author) |
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| Files: |  URL - Source URL, visit https://www.nature.com/articles/s41598-023-46893-4
 PDF - Presentation file, download (1,53 MB)
MD5: 375950014779F2316D27DAFE3DA1F1C6
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | Vascular endothelial growth factor (VEGF)-A induces endothelial hyperpermeability, but the molecular
pathways remain incompletely understood. Endothelial nitric oxide synthase (eNOS) regulates acute
efects of VEGF-A on permeability of endothelial cells (ECs), but it remains unknown whether and how
eNOS regulates late efects 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 fndings
underscore the complexity of VEGF-A-induced permeability pathways in ECs and the role of eNOS
therein, and demonstrate that diferent pathways are activated depending on the EC phenotype.
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| Keywords: | endocytosis, RNAi, hyperpermeability |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 05.12.2023 |
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| Year of publishing: | 2023 |
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| Number of pages: | str. 1-14 |
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| Numbering: | Vol. 13, [article no.] 21436 |
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| PID: | 20.500.12556/DiRROS-19306  |
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| UDC: | 577.2 |
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| ISSN on article: | 2045-2322 |
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| COBISS.SI-ID: | 190987779 |
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| Note: | Soavtorji: Shahan Darwesh, Yasmin I. Habani, Maxime Cammeraat, Paola Serrano Martinez, Mathilda E. van Breest Smallenburg, JiaY. Zheng , Ilse M. C.Vogels , Cornelis J. F. van Noorden, Reinier O. Schlingemann1 & Ingeborg Klaassen;
Nasl. z nasl. zaslona;
Opis vira z dne 31. 3. 2024;
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| Publication date in DiRROS: | 15.07.2024 |
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| Views: | 354 |
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| Downloads: | 228 |
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