Intussusceptive angiogenesis: its emergence, its characteristics, and its significance.

This review shall familiarize the reader with the various aspects of intussusceptive angiogenesis (IA). The basic event in IA is the formation of transvascular tissue pillars. Depending on location, timing, and frequency of pillar emergence, the IA process has different outcomes. In capillaries, a primary IA function is to expand the capillary bed in size and complexity (intussusceptive microvascular growth). It represents an alternative to capillary sprouting. Highly ordered pillar formation in a developing capillary network leads to the formation of vascular trees (intussusceptive arborization). In small arteries and veins, pillar formation at the vessels' branching angles leads either to remodeling of the branching geometry or even to vascular pruning (intussusceptive branching remodeling). It appears essential that future angiogenic research considers always both phenomena, sprouting and intussusception. Vascularization of tissues, organs, and tumors rely heavily on both mechanisms; neglecting one or the other would obscure our understanding of the angiogenesis process.