VEGF withdrawal induces vascular remodelling and pruning via intussusception

Once the capillary plexuses have been formed, they undergo a process of intensive remodelling including formation of feeding vessels and adaptation of the vascular branching morphology. We used the chicken chorioallantoic membrane (CAM) and the chick kidney demonstrating the effects of VEGF withdrawal. We observed emergence of remodelling and adaptation by formation of transvascular tissue pillars i.e. intussusception at vascular bifurcations (intussusceptive branching remodelling = IBR). IBR occurred by formation of pillars close to a bifurcation angle. The pillars increased in girth until they merged with the connective tissue in the bifurcation angle. Morphometric investigations demonstrated that IBR resulted in optimisation of the branching geometry such that optimality was augmented by minimization of pumping energy and building material. The formation of multiple eccentric pillars and their subsequent successive fusions meant that IBR was also extensively involved in vascular pruning, a process that results in reduction of the number of vascular branches. Putatively, sub‐maintenance doses of VEGF cause vascular remodelling. Application of fibrin matrices containing VEGF121 and 165 on CAM caused a pronounced angiogenic response. Subsequent removal of the matrices resulted in extensive intussusceptive vascular pruning, with a following reduction in the number of small arteries and veins. Local application of VEGF inhibitors, induced similar changes in the CAM. Relation between VEGF withdrawal and intussusceptive pruning was also found in the developing kidney. Disappearance of the pro‐ and mesonephrons is related to the VEGF down regulation followed by massive intussusceptive pruning. We conclude that intussusception plays a crucial role in vascular tree remodelling and pruning in response to angiogenic factors and changing hemodynamic conditions. Funded by SNF 3100A0‐104000/1