The data obtained demonstrate that after the sprouting phase and formation of the primitive capillary meshwork, the hemodynamic conditions enhance intussusceptive segregation of hierarchical vascular tree
Intussusceptive angiogenesis (IA) is a complementary method to sprouting angiogenesis (SA). The hallmark of IA is the formation of trans-capillary tissue pillars, their fusion and remodelling of the vascular plexus. In this study, we investigate the formation of the zebrafish caudal vein plexus (CVP) in Tg(fli1a:eGFP) y7 and the synergistic interaction of IA and SA in crafting the archetypical angioarchitecture of the CVP.
Dynamic in vivo observations and quantitative analyses revealed that the primitive CVP during development was initiated through SA. Further vascular growth and remodelling occurred by IA. Intussusception contributed to the expansion of the CVP by the formation of new pillars. Those pillars arose in front of the already existing ones, and in a subsequent step, the serried pillars elongated and fused together. This resulted in the segregation of larger vascular segments and remodelling of the disorganized vascular meshwork into the hierarchical tree-like arrangement. Blood flow was the main driving force for IA, particularly shear stress geometry at the site of pillar formation and fusion.
Computational simulations based on hemodynamics showed a drop in shear stress levels at locations of new pillar formation, pillar elongation and fusion. Correlative 3D serial block-face scanning electron microscopy confirmed the morphological substrate of the phenomena of the pillar formation observed in vivo. The data obtained demonstrate that after the sprouting phase and formation of the primitive capillary meshwork, the hemodynamic conditions enhance intussusceptive segregation of hierarchical vascular tree i.e. intussusceptive arborization resulting in complex vascular structures with specific angioarchitecture.
This study was conducted by