Vascular remodeling by intussusceptive angiogenesis

Abstract

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.

A New Mechanism for Pillar Formation during Tumor-Induced Intussusceptive Angiogenesis: Inverse Sprouting

“…4,5 In these models, protrusion of the vascular wall into the lumen, interendothelial adherence, and perforation of the endothelial bilayer by reorganization of the interendothelial junctions were the first events. These events were promptly followed by the appearance of perivascular cells within the pillar.…”

“…Interestingly, although transluminal pillars were formed under different conditions in our study (ie, during tumor vascularization because there were no signs of pillar formation in healing cutaneous wounds), the initial size of pillars (approximately 2.5 m) was remarkably similar to that observed in nontumorous conditions (Ͻ2.5 m). 4,5 Intussusceptive angiogenesis, which results in high local vascular density, is initiated by rapid nascent pillar formation, followed by slow pillar enlargement (a noninvasive process for which extensive connective tissue synthesis is required). Therefore, one reason for the lack of intussusceptive angiogenesis in skin wounds could be that neither pillar development nor the intussusceptive angiogenesis itself is an invasive process; thus, both are not suitable to vascularize initially avascular spaces (such as a fibrin clot).…”

Deficiency of Zonula Occludens-1 Causes Embryonic Lethal Phenotype Associated with Defected Yolk Sac Angiogenesis and Apoptosis of Embryonic Cells

“…Although the connection of yolk sac mesodermal and endodermal layers, an important angiogenesis process (Drake and Little, 1995;Djonov et al, 2003;Coultas et al, 2005), was significantly inhibited by a deficiency of ZO-1, it remains unclear how the absence of ZO-1 and the mislocalization of JAM-A were related with defective angiogenesis in Tjp1 Ϫ/Ϫ embryos. It is possible that ZO-1, JAM-A, or both played an important role in the remodeling for connection between the yolk sac mesoderm and endoderm layers in angiogenesis by directly or indirectly organizing some aspects of cell-cell adhesion in such a way that its deficiency inhibited angiogenesis.…”

Partial persistence of exercise-induced myocardial angiogenesis following 4-week detraining in the rat

“…The mechanisms underlying exercise-induced angiogenesis and vasculogenesis have been extensively reviewed in Conway et al (2001), Gustafsson and Kraus (2001), Brown (2003), Djonov et al (2003), Helisch and Schaper (2003), Kutryk and Stewart (2003), Prior et al (2004), Bloor (2005) and Yoon et al (2004). Despite general agreement about exercise-induced angiogenesis in skeletal muscle, myocardial angiogenesis is less established, especially after moderate exercise in post-pubertal animals (Hudlicka et al 1992;Brown 2003).…”