Vascular remodeling by intussusceptive angiogenesis
- 1.1k Downloads
Intussusception (growth within itself) is an alternative to the sprouting mode of angiogenesis. The protrusion of opposing microvascular walls into the capillary lumen creates a contact zone between endothelial cells. The endothelial bilayer is perforated, intercellular contacts are reorganized, and a transluminal pillar with an interstitial core is formed, which is soon invaded by myofibroblasts and pericytes leading to its rapid enlargement by the deposition of collagen fibrils. Intussusception has been implicated in three processes of vascular growth and remodeling. (1) Intussusceptive microvascular growth permits rapid expansion of the capillary plexus, furnishing a large endothelial surface for metabolic exchange. (2) Intussusceptive arborization causes changes in the size, position, and form of preferentially perfused capillary segments, creating a hierarchical tree. (3) Intussusceptive branching remodeling (IBR) leads to modification of the branching geometry of supplying vessels, optimizing pre- and postcapillary flow properties. IBR can also lead to the removal of branches by pruning in response to changes in metabolic needs. None of the three modes requires the immediate proliferation of endothelial cells but rather the rearrangement and plastic remodeling of existing ones. Intussusception appears to be triggered immediately after the formation of the primitive capillary plexus by vasculogenesis or sprouting. The advantage of this mechanism of growth over sprouting is that blood vessels are generated more rapidly in an energetically and metabolically more economic manner, as extensive cell proliferation, basement membrane degradation, and invasion of the surrounding tissue are not required; the capillaries thereby formed are less leaky. This process occurs without disrupting organ function. Improvements in our understanding of the process should enable the development of novel pro- and anti-angiogenic therapeutic treatments.
KeywordsAngiogenesis Non-sprouting angiogenesis Intussusceptive microvascular growth Intussusceptive arborization Intussusceptive branching remodeling Pruning Sprouting
We thank K. Sala, B. de Breuyn, B. Haenni, K. Babl, and B. Krieger for their technical assistance, S.A. Tschanz for the three-dimensional reconstruction of pillars, and E. de Peyer for art work.
- Auerbach R, Kubai L, Knighton D, Folkman J (1974) A simple procedure for the long-term cultivation of chicken embryos. Dev Biol 41:391–394Google Scholar
- Bergers G, Benjamin LE (2003) Angiogenesis: tumorigenesis and the angiogenic switch. Nat Rev Cancer 3:401–410Google Scholar
- Clark E, Clark E (1939) Microscopic observations of the growth of blood capillaries in the living mammal. Am J Anat 64:251–299Google Scholar
- Djonov V, Schmid M, Tschanz SA, Burri PH (2000a) Intussusceptive angiogenesis: its role in embryonic vascular network formation. Circ Res 86:286–292Google Scholar
- Djonov VG, Galli AB, Burri PH (2000b) Intussusceptive arborization contributes to vascular tree formation in the chick chorio-allantoic membrane. Anat Embryol (Berl) 202:347–357Google Scholar
- Groningen JP van, Wenink AC, Testers LH (1991) Myocardial capillaries: increase in number by splitting of existing vessels. Anat Embryol (Berl) 184:65–70Google Scholar
- Patan S, Haenni B, Burri PH (1993) Evidence for intussusceptive capillary growth in the chicken chorio-allantoic membrane (CAM). Anat Embryol (Berl) 187:121–130Google Scholar
- Shin D, Garcia-Cardena G, Hayashi S, Gerety S, Asahara T, Stavrakis G, Isner J, Folkman J, Gimbrone MA Jr, Anderson DJ (2001) Expression of ephrinB2 identifies a stable genetic difference between arterial and venous vascular smooth muscle as well as endothelial cells, and marks subsets of microvessels at sites of adult neovascularization. Dev Biol 230:139–150PubMedGoogle Scholar
- Zeltner TB, Caduff JH, Gehr P, Pfenninger J, Burri PH (1987) The postnatal development and growth of the human lung. I. Morphometry. Respir Physiol 67:247–267Google Scholar
- Zhang ZG, Zhang L, Tsang W, Soltanian-Zadeh H, Morris D, Zhang R, Goussev A, Powers C, Yeich T, Chopp M (2002) Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J Cereb Blood Flow Metab 22:379–392PubMedGoogle Scholar