Angiogenesis: an adaptive dynamic biological patterning problem

PLoS Comput Biol. 2013;9(3):e1002983. doi: 10.1371/journal.pcbi.1002983. Epub 2013 Mar 21.

Abstract

Formation of functionally adequate vascular networks by angiogenesis presents a problem in biological patterning. Generated without predetermined spatial patterns, networks must develop hierarchical tree-like structures for efficient convective transport over large distances, combined with dense space-filling meshes for short diffusion distances to every point in the tissue. Moreover, networks must be capable of restructuring in response to changing functional demands without interruption of blood flow. Here, theoretical simulations based on experimental data are used to demonstrate that this patterning problem can be solved through over-abundant stochastic generation of vessels in response to a growth factor generated in hypoxic tissue regions, in parallel with refinement by structural adaptation and pruning. Essential biological mechanisms for generation of adequate and efficient vascular patterns are identified and impairments in vascular properties resulting from defects in these mechanisms are predicted. The results provide a framework for understanding vascular network formation in normal or pathological conditions and for predicting effects of therapies targeting angiogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Vessels / anatomy & histology
  • Blood Vessels / growth & development
  • Blood Vessels / pathology
  • Computational Biology
  • Male
  • Models, Cardiovascular*
  • Neovascularization, Pathologic
  • Neovascularization, Physiologic / physiology*
  • Oxygen / metabolism
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Oxygen