Development and differentiation of endothelium

Vascular endothelial cells play an important role in tissue homeostasis, fibrinolysis, and coagulation; blood-tissue exchange, vasotonus regulation, blood cell activation, and migration; and the vascularization of tissues. The formation of new blood vessels comprises two distinct steps: vasculogenesis, the in situ assembly of capillaries, and angiogenesis, the sprouting of capillaries from preexisting ones. Vascular endothelial growth factor (VEGF) is essential for vasculogenesis and angiogenesis. Its expression is high in the embryonic brain and kidney when angiogenesis occurs and low in the adult brain when angiogenesis is absent. In the kidney, VEGF expression remains high in glomerular podocytes even in the adult. VEGF receptors 1 and 2 (fit-1 and flk-1) are endothelial-specific receptor tyrosine kinases. Similar to the ligand, expression of these receptors is high during brain and kidney angiogenesis, low in adult brain endothelium, but high in adult glomerular endothelium. Because VEGF is also a vascular permeability factor, the expression in the adult correlates with the low permeability of blood-brain barrier endothelium and the high permeability of fenestrated glomerular endothelium. Although fenestrae formation can be induced in vitro by VEGF and a basal lamina-type extracellular matrix, blood-brain barrier characteristics seem to require the presence of still unknown brain-derived factors.