Harold F Dvorak

Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts

VEGF-A is the founding member of the VPF/VEGF family of proteins that also includes VEGFs B, C, and D as well as placenta growth factor (PlGF) and a related viral protein, VEGF-E. 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. 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), VEGF-A is also an endothelial cell motogen and mitogen, profoundly alters the pattern of endothelial cell gene expression, and protects endothelial cells from apopto-sis and senescence. Recently, VEGF-A has been found to have additional critical roles in hematopoiesis, in expansion and differentiation of bone marrow endothelial cell precursors, and in development and maintenance of the nervous system. The functions of other VPF/VEGF family members have been less well characterized. However, VEGFs C and D are essential for development of the lymphatic system, VEGF-B has a role in the development of coronary arteries, and PlGF has important roles in pathological angiogenesis.

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