Angiogenic Factors produced by Hypoxic Cells are a leading driver of Anastomoses in Sprouting Angiogenesis---a computational study

TL;DR

This computational study shows that hypoxia-induced angiogenic factors significantly promote vessel anastomosis in 2D and 3D models, influencing network morphology and resilience.

Contribution

It introduces a systematic computational approach demonstrating the role of hypoxia-driven factors in vessel anastomosis formation.

Findings

Hypoxia-induced factors promote anastomosis in simulations.

Network morphology depends on tissue cell distribution and growth factor concentration.

Vascular networks show increased resilience to cell proliferation and chemotactic variations.

Abstract

Angiogenesis - the growth of new blood vessels from a pre-existing vasculature - is key in both physiological processes and on several pathological scenarios such as cancer progression or diabetic retinopathy. For the new vascular networks to be functional, it is required that the growing sprouts merge either with an existing functional mature vessel or with another growing sprout. This process is called anastomosis. We present a systematic 2D and 3D computational study of vessel growth in a tissue to address the capability of angiogenic factor gradients to drive anastomosis formation. We consider that these growth factors are produced only by tissue cells in hypoxia, i.e. until nearby vessels merge and become capable of carrying blood and irrigating their vicinity. We demonstrate that this increased production of angiogenic factors by hypoxic cells is able to promote vessel anastomoses events in both 2D and 3D. The simulations also verify that the morphology of these networks has an increased resilience toward variations in the endothelial cell's proliferation and chemotactic response. The distribution of tissue cell`s and the concentration of the growth factors they produce are the major factors in determining the final morphology of the network.