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

Cells

Lucía Recio-Poveda¹  Virginia Albiñana¹  Luisa M. Botella¹  Isabel de Rojas-P¹  Angel M. Cuesta¹  Nikita Popov²  Thales Kronenberger²  Lyudmyla Taranets² 

[1] Centro de Investigaciones Biológicas Margaritas Salas, 28040 Madrid, Spain;Department of Internal Medicine VIII, University Hospital Tübingen, Otfried-Müller-Strasse 14, 72076 Tübingen, Germany;

关键词: VHL;    BOECs;    endothelial cells;    ROS;    angiogenesis;    wound healing;   

DOI  :  10.3390/cells10092313

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown