The Diverse Roles of Integrins and Their Ligands in Angiogenesis

The circulatory system is the first organ establishedduring vertebrate development and is essential for life.During later development and in adult life, the vasculature is a dynamic system, generating additional vessels inresponse to need. It is generally agreed that the initial vascular network arises by a process termed vasculogenesisin which vascular precursors, angioblasts, generate endothelial cells that migrate and coalesce into the primitivevasculature. Later development of the vascular tree, andessentially all new vessel formation in adult life, arise bybranching from this initial network and its derivatives.This process is usually called angiogenesis, although thatencompasses diverse processes such as sprouting,branching, subdivision of existing vessels by bridging,and intussusception (Beck and D'Amore 1997; Carmelietand Collen 1997; Risau 1997). Both vasculogenesis andangiogenesis, in their various forms, require cell proliferation and migration and cell–cell adhesion to form the endothelial tubes of the vasculature. Those endothelialtubes are surrounded by a basement membrane (BM), andadhesion of the endothelial cells to this extracellular matrix (ECM) is also required. Furthermore, additional cellssurround the basic endothelial tubes and interact with theBM of the vessels. Depending on the vessel type, these"mural cells" are termed pericytes (small vessels) orsmooth muscle cells (larger vessels), although they likelyarise from the same cell lineage. These mural cells mustalso migrate to the developing vessels and form adhesivecontacts with the BMs of the vasculature. Therefore, cellmigration and cell–cell and cell–matrix adhesion are central to vascular development and remodeling. Much ofthe cell–matrix adhesion occurs via members of the integrin family, which are also involved in migration of thecells to form the vessels. Other cell adhesion molecules,such as cadherins, and cell interaction receptors, such asthe ephrin, Eph, and Notch families, are also involved andmay interact with the integrins. In this paper, we focus onintegrins and their ligands, predominantly ECM glycoproteins, and consider the diverse roles that they play invascular development and remodeling...