Angiogenesis: Basics of Vascular Biology

Angiogenesis occurs by two mechanisms sprouting angiogenesis and intussusceptive angiogenesis. Intussusceptive angiogenesis starts with the formation of an intravascular pillar, which can be extended, so that a vessel tube becomes separated in two parallel branches. Sprouting angiogenesis regards the outward formation of small new vascular branches that starts via invasion of endothelial sprouts into the extracellular matrix. These sprouts are led by a tip cell that strongly responds to exogenous angiogenic factors, of which VEGF-A is the most prominent. This chapter describes molecular steps and metabolic responses that occur within the tip cell and the subsequent signaling that alters the behavior of the adjacent stalk cells. Subsequently, lumen formation, anastomosis, and restoration of perfusion occur, as well as selective removal of excess vascular branches by pruning. The process of angiogenesis is enforced by postnatal vasculogenesis, which represents the recruitment of circulating true endothelial progenitor cells (late outgrowth EPCs or endothelial colony forming cells) to an area in need of blood supply, and is further supported by recruitment of myeloid early-outgrowth EPCs that have an auxiliary function. The detailed studies on the sprouting process itself have to be placed into a (patho)physiological context to be able to generate functional microvascular networks. From combined computational modeling and experimental studies it has become clear that formation of a new microvascular network requires the mutual interplay between sprouting, redistribution (remodeling), and pruning of endothelial tubules into a functional vascular bed.