Regulation of angiogenesis by extracellular matrix: the growth and the glue

Angiogenesis is broadly defined as the growth of new capillaries from extant vessels and constitutes a major part of developmental morphogenesis, response to injury and pathogenesis. Two regulatory pathways are proposed by which angiogenesis is thought to proceed.

The proliferative pathway depends on various cytokines and other factors that both stimulate and inhibit the proliferation of endothelial cells. One of these components, secreted protein acidic and rich in cysteine (SPARC), might function at several levels to control the progression of neovessels. Proteolysis of this component (e.g. by plasmin) results in the release of peptides containing the sequence Gly-His-Lys, which are angiogenic in vitro and in vivo. At later stages of angiogenesis when endothelial cell proliferation ceases, the intact protein is proposed to exert its known inhibitory effect on cell cycle progression.

The morphogenetic pathway depends on the synthesis and assembly of fibrillar type I collagen, which can be used as a template for endothelial cell migration and lumen formation. Endothelial cells interact with substrates of type I collagen and form networks based on the establishment of traction centers. These planar cellular networks, in some respects, resemble developing vasculature in vivo.

An understanding of how proliferation and morphogenesis are controlled during vascular growth is likely to reconcile several models with respect to the factors that regulate this dynamic process.