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Open AccessArticle

Control of Angiogenesis via a VHL/miR-212/132 Axis

1
Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
2
Department of Nephrology & Hypertension, Division Internal Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
3
Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
4
Department of Medical Genetics, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
5
Netherlands Heart Institute, Catharijnesingel 52, 3511 GC Utrecht, The Netherlands
6
Central Military Hospital Utrecht, Lundlaan 1, 3584 EZ Utrecht, The Netherlands
7
UMC Utrecht Regenerative Medicine Center, University Medical Center, 3584 CT Utrecht, The Netherlands
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(4), 1017; https://doi.org/10.3390/cells9041017
Received: 20 March 2020 / Revised: 9 April 2020 / Accepted: 15 April 2020 / Published: 19 April 2020
(This article belongs to the Special Issue Arteriogenesis and Therapeutic Neovascularization)
A common feature of tumorigenesis is the upregulation of angiogenesis pathways in order to supply nutrients via the blood for the growing tumor. Understanding how cells promote angiogenesis and how to control these processes pharmaceutically are of great clinical interest. Clear cell renal cell carcinoma (ccRCC) is the most common form of sporadic and inherited kidney cancer which is associated with excess neovascularization. ccRCC is highly associated with biallelic mutations in the von Hippel–Lindau (VHL) tumor suppressor gene. Although upregulation of the miR-212/132 family and disturbed VHL signaling have both been linked with angiogenesis, no evidence of a possible connection between the two has yet been made. We show that miRNA-212/132 levels are increased after loss of functional pVHL, the protein product of the VHL gene, in vivo and in vitro. Furthermore, we show that blocking miRNA-212/132 with anti-miRs can significantly alleviate the excessive vascular branching phenotype characteristic of vhl−/− mutant zebrafish. Moreover, using human umbilical vascular endothelial cells (HUVECs) and an endothelial cell/pericyte coculture system, we observed that VHL knockdown promotes endothelial cells neovascularization capacity in vitro, an effect which can be inhibited by anti-miR-212/132 treatment. Taken together, our results demonstrate an important role for miRNA-212/132 in angiogenesis induced by loss of VHL. Intriguingly, this also presents a possibility for the pharmaceutical manipulation of angiogenesis by modulating levels of MiR212/132. View Full-Text
Keywords: VHL loss of function; microRNA-212/132; angiogenesis VHL loss of function; microRNA-212/132; angiogenesis
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MDPI and ACS Style

Lei, Z.; Klasson, T.D.; Brandt, M.M.; van de Hoek, G.; Logister, I.; Cheng, C.; Doevendans, P.A.; Sluijter, J.P.G.; Giles, R.H. Control of Angiogenesis via a VHL/miR-212/132 Axis. Cells 2020, 9, 1017. https://doi.org/10.3390/cells9041017

AMA Style

Lei Z, Klasson TD, Brandt MM, van de Hoek G, Logister I, Cheng C, Doevendans PA, Sluijter JPG, Giles RH. Control of Angiogenesis via a VHL/miR-212/132 Axis. Cells. 2020; 9(4):1017. https://doi.org/10.3390/cells9041017

Chicago/Turabian Style

Lei, Zhiyong; Klasson, Timothy D.; Brandt, Maarten M.; van de Hoek, Glenn; Logister, Ive; Cheng, Caroline; Doevendans, Pieter A.; Sluijter, Joost P.G.; Giles, Rachel H. 2020. "Control of Angiogenesis via a VHL/miR-212/132 Axis" Cells 9, no. 4: 1017. https://doi.org/10.3390/cells9041017

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