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Glycolytic regulation of cell rearrangement in angiogenesis

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Item Type:Article
Title:Glycolytic regulation of cell rearrangement in angiogenesis
Creators Name:Cruys, B. and Wong, B.W. and Kuchnio, A. and Verdegem, D. and Cantelmo, A. R. and Conradi, L.C. and Vandekeere, S. and Bouché, A. and Cornelissen, I. and Vinckier, S. and Merks, R.M.H. and Dejana, E. and Gerhardt, H. and Dewerchin, M. and Bentley, K. and Carmeliet, P.
Abstract:During vessel sprouting, endothelial cells (ECs) dynamically rearrange positions in the sprout to compete for the tip position. We recently identified a key role for the glycolytic activator PFKFB3 in vessel sprouting by regulating cytoskeleton remodelling, migration and tip cell competitiveness. It is, however, unknown how glycolysis regulates EC rearrangement during vessel sprouting. Here we report that computational simulations, validated by experimentation, predict that glycolytic production of ATP drives EC rearrangement by promoting filopodia formation and reducing intercellular adhesion. Notably, the simulations correctly predicted that blocking PFKFB3 normalizes the disturbed EC rearrangement in high VEGF conditions, as occurs during pathological angiogenesis. This interdisciplinary study integrates EC metabolism in vessel sprouting, yielding mechanistic insight in the control of vessel sprouting by glycolysis, and suggesting anti-glycolytic therapy for vessel normalization in cancer and non-malignant diseases.
Keywords:Adenosine Triphosphate, CD, Antigens, Cadherins, Computer Simulation, Gene Knockdown Techniques, Glycolysis, Human Umbilical Vein Endothelial Cells, Indoles, Biological, Models, Physiologic, Neovascularization, Phosphofructokinase-2, Pseudopodia, Pyridines, Vascular Endothelial Growth Factor A
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:12240
Date:20 July 2016
Official Publication:https://doi.org/10.1038/ncomms12240
PubMed:View item in PubMed

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