Selective induction of sprouting and intussusception is associated with the concentration distributions of oxygen and hypoxia-induced VEGF

Sprouting and intussusception are two important modes of capillary angiogenesis, the mechanisms of selective induction of which remain unclear. In this study, we focus on the two developing tissues of yolk sac and skeletal muscle of 2-week-old rat and try to explain the mechanisms to induce selectively sprouting and intussusception in a new way to combine numerical calculation, experimental observations and schematic simulation. We propose the concept of capillary network unit and show that the concentration and gradient of oxygen/hypoxia-induced VEGF around straight segments are lower/higher than that around vascular bifurcations; sprouting mainly occurs at straight segments and intussusception at vascular bifurcations. The results indicate that the locations susceptible to sprouting and intussusception are determined by the distribution characteristics of oxygen/hypoxia-induced VEGF in the capillary network unit. Furthermore, it is considered that the flow dynamics at these locations also play important roles, namely laminar flow at straight segments promotes sprouting, and flow disruption at bifurcations promotes intussusception. Our work suggests the presence of the location preference for sprouting and intussusception, and provides a new research perspective to reveal its core mechanisms. [Display omitted] •Polygonal capillary loop as a unit is an epitome of capillary network system.•Method to identify intussusception that occurs at bifurcation is proposed.•Sprouting occurs at straight segments, intussusception at vascular bifurcations.•Sprouting may be due to high degree of hypoxia and laminar flow.•Intussusception may be due to low degree of hypoxia and flow disruption.