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The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease

Von Hippel–Lindau disease (VHL) is a rare hereditary disease characterized by the predisposal to develop different types of highly vascularized tumors. VHL patients carry a VHL mutation that causes partial lack of functional VHL protein (pVHL) in all cells, and a total lack thereof in cells harborin...

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Autores principales: de Rojas-P, Isabel, Albiñana, Virginia, Taranets, Lyudmyla, Recio-Poveda, Lucía, Cuesta, Angel M., Popov, Nikita, Kronenberger, Thales, Botella, Luisa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465092/
https://www.ncbi.nlm.nih.gov/pubmed/34571962
http://dx.doi.org/10.3390/cells10092313
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author de Rojas-P, Isabel
Albiñana, Virginia
Taranets, Lyudmyla
Recio-Poveda, Lucía
Cuesta, Angel M.
Popov, Nikita
Kronenberger, Thales
Botella, Luisa M.
author_facet de Rojas-P, Isabel
Albiñana, Virginia
Taranets, Lyudmyla
Recio-Poveda, Lucía
Cuesta, Angel M.
Popov, Nikita
Kronenberger, Thales
Botella, Luisa M.
author_sort de Rojas-P, Isabel
collection PubMed
description Von Hippel–Lindau disease (VHL) is a rare hereditary disease characterized by the predisposal to develop different types of highly vascularized tumors. VHL patients carry a VHL mutation that causes partial lack of functional VHL protein (pVHL) in all cells, and a total lack thereof in cells harboring a second hit mutation. Absence of pVHL generates a prolonged state of pseudo-hypoxia in the cell due to accumulation of hypoxia inducible factor, an important transcription factor regulating pro-tumorigenic genes. The work here presented focuses on characterizing the endothelium of VHL patients, by means of blood outgrowth endothelial cells (BOECs). Transcriptome analysis of VHL-derived BOECs, further supported by in vitro assays, shows that these cells are at a disadvantage, as evidenced by loss of cell adhesion capacity, angiogenesis defects, and immune response and oxidative metabolic gene downregulation, which induce oxidative stress. These results suggest that the endothelium of VHL patients is functionally compromised and more susceptible to tumor development. These findings contribute to shedding light on the vascular landscape of VHL patients preceding the second hit mutation in the VHL gene. This knowledge could be useful in searching for new therapies for these patients and other vascular diseases.
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spelling pubmed-84650922021-09-27 The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease de Rojas-P, Isabel Albiñana, Virginia Taranets, Lyudmyla Recio-Poveda, Lucía Cuesta, Angel M. Popov, Nikita Kronenberger, Thales Botella, Luisa M. Cells Article Von Hippel–Lindau disease (VHL) is a rare hereditary disease characterized by the predisposal to develop different types of highly vascularized tumors. VHL patients carry a VHL mutation that causes partial lack of functional VHL protein (pVHL) in all cells, and a total lack thereof in cells harboring a second hit mutation. Absence of pVHL generates a prolonged state of pseudo-hypoxia in the cell due to accumulation of hypoxia inducible factor, an important transcription factor regulating pro-tumorigenic genes. The work here presented focuses on characterizing the endothelium of VHL patients, by means of blood outgrowth endothelial cells (BOECs). Transcriptome analysis of VHL-derived BOECs, further supported by in vitro assays, shows that these cells are at a disadvantage, as evidenced by loss of cell adhesion capacity, angiogenesis defects, and immune response and oxidative metabolic gene downregulation, which induce oxidative stress. These results suggest that the endothelium of VHL patients is functionally compromised and more susceptible to tumor development. These findings contribute to shedding light on the vascular landscape of VHL patients preceding the second hit mutation in the VHL gene. This knowledge could be useful in searching for new therapies for these patients and other vascular diseases. MDPI 2021-09-04 /pmc/articles/PMC8465092/ /pubmed/34571962 http://dx.doi.org/10.3390/cells10092313 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
de Rojas-P, Isabel
Albiñana, Virginia
Taranets, Lyudmyla
Recio-Poveda, Lucía
Cuesta, Angel M.
Popov, Nikita
Kronenberger, Thales
Botella, Luisa M.
The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
title The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
title_full The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
title_fullStr The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
title_full_unstemmed The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
title_short The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
title_sort endothelial landscape and its role in von hippel–lindau disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465092/
https://www.ncbi.nlm.nih.gov/pubmed/34571962
http://dx.doi.org/10.3390/cells10092313
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