Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies

JOURNAL OF THEORETICAL BIOLOGY

卷:456

Article

Lakatos, Dora¹  Somfai, Ellak²  Mehes, Elod¹  Czirok, Andras^1,3 

[1] Eotvos Lorand Univ, Dept Biol Phys, Budapest, Hungary

[2] Hungarian Acad Sci, Wigner Res Ctr Phys, Inst Solid State Phys & Opt, Budapest, Hungary

[3] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA

关键词: VEGF;    Vasculature;    Pattern formation;    Reaction-diffusion;   

DOI  :  10.1016/j.jtbi.2018.08.005

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free