The formation of blood vessels occurs either by in situ differentiation of endothelial cell precursors (Angioblasts) and association of these cells to form primitive vessels, a process called Vasculogenesis, or by growth of preexisting vessels, a process ...called Angiogenesis. Vasculogenesis establishes the primary vascular plexus of the early embryo, whereas development of blood vessels during later embryogenesis and adult life occurs primarily by Angiogenesis. Angiogenesis is an integral feature of capillary sprouts from preexisting blood vessels. It is typically quiescent in the adult, except for pathological situations (e.g., wound healing, diabetic retinopathy, rheumatoid arthritis, cardiac ischemia, psoriasis, tumor growth) and during menstrual cycle-specific physiological processes in the female reproductive system (e.g., ovulation, endometrial growth, implantation, placentation). Once blood vessels have been established, endothelial cells undergo tissue-specific changes to generate numerous types of functionally distinct vessels as organs differentiate. These processes require that endothelial cells respond to a variety of extracellular signals that activate receptors responsible for growth and differentiation. VEGF (Vascular Endothelial Growth Factor), Angiopoietin and Ephrin are key molecules in the promotion of angiogenesis via activation of the VEGFR (VEGF Receptor), TIE and Ephrin expressed on vascular endothelial cells, respectively. VEGF signaling plays a major role in promoting the proliferation and differentiation of the endothelial lineage from the earliest stages of development, whereas the Angiopoietin/TIE2 pathway acts slightly later to promote the recruitment of supporting cells and vessel stabilization. However, the complex patterning of the developing vasculature also requires specific vascular roles for the components of other signaling pathways, including the Ephrin, TGF-Beta (Transforming Growth Factor- Beta), PDGF (Platelet-Derived Growth Factor), FGF (Fibroblast Growth Factor),and Delta-Notch Pathways. VEGF is a heparin-binding homodimeric glycoprotein that acts via endothelial-specific receptor tyrosine kinases, VEGFR1 (Flt1), VEGFR2 (KDR/Flk1), and VEGFR3 (Flt4). Besides VEGFA, the VEGF family of growth factors currently contains five other known members, namely PlGF (Placenta Growth Factor), VEGFB, VEGFC, VEGF-D and orf viral VEGF homologs.
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