Simulation of angiogenesis, remodeling and pruning in microvascular networks

Abstract

In the microcirculation, vessel formation (angiogenesis), structural adaptation (remodeling), and regression (pruning) redistribute flow in response to varying demands. Here, previously developed theoretical models for remodeling in response to pressure, shear stress and local oxygen level (PO2) are extended to include vessel sprouting, interconnection and pruning. A diffusible growth factor (GF) is assumed to be produced in hypoxic tissue. For given network geometry, the blood flow distribution and the resulting PO2 and GF fields are computed. The probability of sprout formation depends on local GF concentration, and the direction of sprout growth depends on GF gradient. Pruning occurs when diameter drops below 3 μm. In simulations starting with a sparse network and tissue hypoxia, vascular density first increased, with many non-flowing segments. Redundant vessels then dropped out, yielding stable and efficient network structures with little or no hypoxia, resembling structures observed in the rat mesentery. Both remodeling and pruning were found to be necessary for formation of functional and efficient networks. Supported by NIH HL034555.