Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 456, Issue -, Pages 261-278Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2018.08.005
Keywords
VEGF; Vasculature; Pattern formation; Reaction-diffusion
Categories
Funding
- US National Institute of Health [GM102801]
- Hungarian National Research Development and Innovation Office [OTKA 118119 ANN]
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Vascular patterning is a key process during development and disease. The diffusive decoy receptor sVEGFRI (sFlt1) is a known regulator of endothelial cell behavior, yet the mechanism by which it controls vascular structure is little understood. We propose computational models to shed light on how vascular patterning is guided by self-organized gradients of the VEGF/sVEGFR1 factors. We demonstrate that a diffusive inhibitor can generate structures with a dense branching morphology in models where the activator elicits directed growth. Inadequate presence of the inhibitor leads to compact growth, while excessive production of the inhibitor blocks expansion and stabilizes existing structures. Model predictions were compared with time-resolved experimental data obtained from endothelial sprout kinetics in fibrin gels. In the presence of inhibitory antibodies against VEGFR1 vascular sprout density increases while the speed of sprout expansion remains unchanged. Thus, the rate of secretion and stability of extracellular sVEGFRI can modulate vascular sprout density. (C) 2018 Elsevier Ltd. All rights reserved.
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