RT Journal Article
T1 The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease
A1 Rojas-P., Isabel de
A1 Albiñana, Virginia
A1 Taranets, Lyudmyla
A1 Recio-Poveda, Lucía
A1 Cuesta Martínez, Ángel
A1 Popov, Nikita
A1 Kronenberger, Thales
A1 Botella, Luisa M.
AB 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.
PB MDPI
SN 2073-4409
YR 2021
FD 2021-09-04
LK https://hdl.handle.net/20.500.14352/114686
UL https://hdl.handle.net/20.500.14352/114686
LA eng
NO de Rojas-P, I.; Albiñana, V.; Taranets, L.; Recio-Poveda, L.; Cuesta, A.M.; Popov, N.; Kronenberger, T.; Botella, L.M. The Endothelial Landscape and Its Role in Von Hippel–Lindau Disease. Cells 2021, 10, 2313. https://doi.org/10.3390/ cells10092313
NO Additionally, V.A. is recipient of a grant from the Spanish Network of Research on Rare Diseases, CIBERER, unit 707
NO Ministerio de Economía y Competitividad (España)
NO Consejo Superior de Investigaciones Científicas (CSIC)
NO Centro de Investigación Biomédica en Red
DS Docta Complutense
RD 5 abr 2025