Molecular regulation of angiogenesis and lymphangiogenesis

The angiogenic growth of blood-vessel capillaries involves sprouting and branching processes that are, in part, controlled by Notch signalling. Gradients of matrix-bound vascular endothelial growth factor A (VEGFA) and other navigational cues are recognized by specialized endothelial tip cells at the distal end of each sprout.The recruitment of bone-marrow-derived monocytic cells to the perivascular space is an important process in adult angiogenesis.The transcription factor prospero-related homeobox-1 (PROX1) is an important regulator of lymphatic endothelial cell differentiation. Sprouting, migration and proliferation of lymphatic endothelial cells is regulated by VEGFC and the VEGF receptor-3 (VEGFR3).Arteriovenous identity is controlled by haemodynamic factors and, at least in some settings, genetic programmes. Such programmes involve the expression of Notch-pathway molecules in arterial endothelial cells whereas venous expression of these genes is actively suppressed by COUP-TFII, a member of the orphan nuclear receptor superfamily.Pericytes and vascular smooth-muscle cells stabilize blood vessels and their incorporation into the vessel wall is an important part of the maturation programme.Defective lymphangiogenic growth and compromised lymphatic endothelial cell identity appear to be interdependent. Known genes that are required for the differentiation of terminal lymphatics and collecting lymphatics as well as the formation of valves are forkhead box-c2 (FOXC2), angiopoietin-2 (ANG2) and ephrin-B2 (EFNB2).