Intussusceptive angiogenesis--the alternative to capillary sprouting.

In contrast to sprouting angiogenesis, which is a well established mode of new blood vessel formation, intussusceptive angiogenesis (IA) is a relatively new concept in vascular biology. It was first discovered in the lung as a means of capillary network growth (intussusceptive microvascular growth). The mechanism consists in the repeated insertion of new slender transcapillary tissue pillars, which subsequently increase in size, thus allowing the capillary network to grow in itself (i.e., by intussusception). It could be shown that IA was present in all organs and species investigated so far, so that it appears to be an ubiquitous phenomenon in vertebrates at least. It was not a surprise therefore to find that IA also played a role in tumour vascularisation. Morphological analysis has yet brought evidence for 6 different modes of pillar formation. They all have in common that, at one time, two endothelial leaflets (e.g. of opposite capillary walls) come into close contact, form new junctional complexes, then thin out to finally give way to the invading interstitial tissue, particularly to fibroblasts, myofibroblasts and pericytes. Once such a transcapillary pillar is formed, it can subsequently grow to the size of a normal intercapillary mesh. The addition of collagen fibrils to the pillar core will stabilize the pillar mechanically. Recent observations allowed to extend the IA concept further: The same structural mechanism of intussusceptive pillar formation was shown to contribute also to the formation of vascular trees (arborisation) and to be involved in vascular remodeling. Although numerous growth factors and receptors have already been suggested as being active in IA, very few hard facts are at present available which would allow to get a comprehensive view of IA regulation.