VEGF A

Abstract

VEGF-A is the founding member of the VPF/VEGF family of proteins that also includes VEGFs B, C and D as well as PlGF (placenta growth factor) and a related viral protein, VEGF-E (Dvorak 2002, 2003; Ferrara et al. 2003; Mukhopadhyay et al. 2007; Bry et al. 2010; Hagberg et al. 2010; Shibuya and Claesson-Welsh 2006; Veikkola and Alitalo 1999). VEGF-A, the subject of this chapter, has critical roles in vasculogenesis and pathological and physiological angiogenesis, acting through receptors (VEGFR-1, VEGFR-2 and neuropilin) that are expressed on vascular endothelium as well as on certain other cell types (Fig. 1) (Shibuya and Claesson-Welsh 2006; Veikkola and Alitalo 1999; Bielenberg et al. 2006). The product of a single gene, VEGF-A is alternatively spliced to form several proteins of different lengths, properties and functions. Originally discovered as a potent vascular permeabilizing factor (VPF) (Senger et al. 1983; Dvorak et al. 1979), VEGF-A is also an endothelial cell motogen and mitogen, profoundly alters the pattern of endothelial cell gene expression, and protects endothelial cells from apoptosis (Benjamin et al. 1999) and senescence (Dvorak 2003). Recently, VEGF-A has been found to have additional critical roles in hematopoiesis and in expansion and differentiation of bone marrow endothelial cell precursors (Seandel et al. 2008), in maintenance of the nervous system (Ruiz de Almodovar et al. 2009), and in development. Mice lacking even one copy of the VEGF-A gene are embryonic lethal (Ferrara et al. 2003; Carmeliet 2003). VEGFs C and D are essential for development of the lymphatic system (Veikkola and Alitalo 1999), VEGF-B has a role in the development of coronary arteries and in fatty acid metabolism (Bry et al. 2010; Hagberg et al. 2010), and PlGF has important roles in pathological angiogenesis (Carmeliet 2003; Luttun et al. 2002). VEGF-A also induces abnormal lymphangiogenesis (Nagy et al. 2002).