Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies. (7th November 2018)

• Record Type: Journal Article
• Authors: Lakatos, Dóra; Somfai, Ellák; Méhes, Előd; Czirók, András
• Is Part Of: Journal of theoretical biology. Volume 456(2018)
• Page Start: 261
• Page End: 278
• Publication Date: 2018-11-07
• Subjects: VEGF -- Vasculature -- Pattern formation -- Reaction-diffusion; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2018.08.005
• Languages: English
• ISSNs: 0022-5193

Abstract

Highlights: Pattern formation guided by an autocrine inhibitor through a reaction-diffusion process. Connected molecular parameters to statistical characteristics of the vasculature. Specific model predictions tested by experiments. 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.