Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies

Dóra Lakatos, Ellák Somfai, Előd Méhes, A. Czirók

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Vascular patterning is a key process during development and disease. The diffusive decoy receptor sVEGFR1 (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 sVEGFR1 can modulate vascular sprout density.

Original languageEnglish
Pages (from-to)261-278
Number of pages18
JournalJournal of Theoretical Biology
Volume456
DOIs
Publication statusPublished - Nov 7 2018

Fingerprint

blood vessels
Inhibitor
Blood Vessels
Branching
branching
Patterning
Endothelial Cells
Secretion
Endothelial cells
Fibrin
Antibody
Antibodies
Regulator
Development Process
Computational Model
Prediction Model
Receptor
Vascular Endothelial Growth Factor A
Gels
Kinetics

Keywords

  • Pattern formation
  • Reaction-diffusion
  • Vasculature
  • VEGF

ASJC Scopus subject areas

  • Statistics and Probability
  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies. / Lakatos, Dóra; Somfai, Ellák; Méhes, Előd; Czirók, A.

In: Journal of Theoretical Biology, Vol. 456, 07.11.2018, p. 261-278.

Research output: Contribution to journalArticle

Lakatos, Dóra ; Somfai, Ellák ; Méhes, Előd ; Czirók, A. / Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies. In: Journal of Theoretical Biology. 2018 ; Vol. 456. pp. 261-278.
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