Activated endothelial cells are capable of assembling threedimensional multicellular structures known as capillary beds in response to several different classes of regulatory macromole-cules. Understanding the regulatory pathways that control growth and regression of new blood vessels is a major goal of researchers in vascular biology today. Regulation of vascular morphogenesis in endothelial cells can be exerted at the levels of cell-cell adhesion, cell-matrix interaction, and control of the cell cycle. The process of angiogenesis, that is, the sprouting of new vessels from a parent microvessel, encompasses various sequential but often coincident stages (Fig. 1). Both angiogenic and anti-angiogenic factors, some of which are listed in Table 1, are believed to target one or more of the stages [1—6]. Thus, regulation of angiogenesis is a dynamic process determined by the balance between counteracting regulatory factors.

The most prominent positive regulators of angiogenesis, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and basic fibroblast growth factor (bFGF or FGF2), signal directly to endothelial cells through their specific receptors, whereas others (PDGF, TGF-/3, and IGF-1) appear to involve indirect mechanisms [1, 2, 7—9]. The mode of action of angiogen-esis inhibitors includes cell cycle arrest (platelet factor-4)[10], inhibition of signal transduction by growth factors (16 kDa prolactin)[11], and/or abrogation of bFGF signaling by truncated high-affinity receptors for bFGF in the circulation and in the basement membrane of some endothelial cells [12]. Recently, a newly-defined class of regulatory macromolecules known as matricellular proteins has received considerable attention, since two of its members (SPARC and thrombospondin 1) have been shown to modulate angiogenesis [6, 13—15]. By definition, these secreted proteins interact with cell-surface receptors, growth factors, and matrix proteins but do not function as structural matrix components. One of the hallmarks of glycoproteins belonging to this group is their ability to disrupt cell-matrix interactions [16, 17]. SPARC can be considered as a prototype for this class of counteradhesive proteins that appear to play dynamic roles in tissue remodeling during normal development or in response to