20.500.12556/DiRROS-19306 Diferential roles of eNOS in late efects ofVEGF‑A on hyperpermeability in diferent types of endothelial cells 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. endocytosis RNAi hyperpermeability true false true Angleški jezik Ni določen Neznano 2024-07-15 10:08:34 2024-07-15 10:08:34 2024-07-16 03:45:13 0000-00-00 00:00:00 2023 0 0 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; str. 1-14 [article no.] 21436 Vol. 13 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2023-12-05 577.2 2045-2322 190987779 https://www.nature.com/articles/s41598-023-46893-4 1 710d0e58-4281-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26627 RAZ_Bosma_Esmeralda_K._2023.pdf RAZ_Bosma_Esmeralda_K._2023.pdf 1 375950014779F2316D27DAFE3DA1F1C6 c18f4e9ad3aa6943a1d46f0c172493b2f3a48c28a8f738871543134147445385 6aa13f8c-4282-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26628 Nacionalni inštitut za biologijo 0 0 0