Complementary and Coordinated Roles of the VEGFs and Angiopoietins during Normal and Pathologic Vascular Formation

Abstract

Mammalian organisms depend on their vasculature todeliver nutrients and oxygen to all of their tissues, totransport products (such as hormones and antibodies)from certain cells to distant parts of the body, and to carryaway waste products. The development of a functioningvasculature, as well as its proper integration into the tissues it serves, depends on myriad interactions and communications between the many cell types involved. Although a large number of signals are involved inmediating these intercellular communications, a greatdeal of focus has been directed to growth factors that aremembers of either the vascular endothelial growth factor(VEGF) family or the angiopoietin family. Why the focuson these two families of growth factors? First of all, thesetwo families of growth factors are unique in that they actvia receptors that are largely restricted to the vasculatureendothelium—this very restricted distribution of their receptors indicates that these two families of growth factorsevolved to play very particular roles specifically involving the vasculature. Moreover, genetic approaches—involving gene knockouts and transgenic overexpression inmice—have spectacularly confirmed the very critical andvery specific roles played by members of these twogrowth factor families during vascular development.Thus, the focus on the VEGFs and angiopoietins seemswell-placed based on their action via vascular-specific receptors and the confirmation of their critical and specificvascular roles based on genetic studies in mice. Since theVEGFs have been extensively dealt with in a number ofexcellent reviews (Eriksson and Alitalo 1999; Ferrara1999; Yancopoulos et al. 2000; Carmeliet et al. 2001),this review highlights work from our laboratory regarding the angiopoietins, although much of this work is presented in the context of the complementary and reciprocal actions of the angiopoietins as compared to theVEGFs...