ABSTRACT

The growth and function of all tissues requires the establishment of an adequate vascular structure. In its absence the tissue becomes deprived of oxygen and nutrients, which cells respond to by producing angiogenic factors that function to recruit new blood vessels into the under-vascularized tissue (Carmeliet 2000; Risau 1997; Saaristo et al., 2000). Of the numerous growth factors that contribute to angiogenesis, vascular endothelial growth factor (VEGF) plays a particularly crucial role as a key regulator of angiogenesis (Kim et al., 1993; Millauer et al., 1994; Shweiki et al., 1992). The importance of VEGF during development, and the requirement for appropriate levels of its expression is demonstrated by the fact that mice bearing a single normal allele for the VEGF gene (i.e. heterozygous for VEGF gene knockout) die in utero due to a failure in vascular development (Carmeliet et al., 1996; Ferrara et al., 1996).