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Title: Partial and Transient Reduction of Glycolysis by PFKFB3 Blockade Reduces Pathological Angiogenesis
Authors: Schoors, Sandra *
De Bock, Katrien *
Cantelmo, Anna Rita *
Georgiadou, Maria *
Ghesquière, Bart
Cauwenberghs, Sandra
Kuchnio, Anna
Wong, Brian W
Quaegebeur, Annelies
Goveia, Jermaine
Bifari, Francesco
Wang, Xingwu
Blanco, Raquel
Tembuyser, Bieke
Cornelissen, Ivo
Bouché, Ann
Vinckier, Stefan
Diaz-Moralli, Santiago
Gerhardt, Holger
Telang, Sucheta
Cascante, Marta
Chesney, Jason
Dewerchin, Mieke #
Carmeliet, Peter # ×
Issue Date: 7-Jan-2014
Publisher: Cell Press
Series Title: Cell Metabolism vol:19 issue:1 pages:37-48
Article number: 10.1016/j.cmet.2013.11.008
Abstract: Strategies targeting pathological angiogenesis have focused primarily on blocking vascular endothelial growth factor (VEGF), but resistance and insufficient efficacy limit their success, mandating alternative antiangiogenic strategies. We recently provided genetic evidence that the glycolytic activator phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) promotes vessel formation but did not explore the antiangiogenic therapeutic potential of PFKFB3 blockade. Here, we show that blockade of PFKFB3 by the small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) reduced vessel sprouting in endothelial cell (EC) spheroids, zebrafish embryos, and the postnatal mouse retina by inhibiting EC proliferation and migration. 3PO also suppressed vascular hyperbranching induced by inhibition of Notch or VEGF receptor 1 (VEGFR1) and amplified the antiangiogenic effect of VEGF blockade. Although 3PO reduced glycolysis only partially and transiently in vivo, this sufficed to decrease pathological neovascularization in ocular and inflammatory models. These insights may offer therapeutic antiangiogenic opportunities.
URI: 
ISSN: 1550-4131
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Exercise Physiology Research Group
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
* (joint) first author
× corresponding author
# (joint) last author

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