Angiogenesis and the action of thalidomide upon angiogenesis. Primitive vessels form through vasculogenesis where endothelial cells coalesce to form primitive tubes through which blood cells pass through. Angiogenesis is the process which elaborates upon these early and newly formed vessels to form vascular networks throughout tissues and the embryo. Angiogenesis is essential for formation of the embryo and continues into adulthood, for example, wound healing. As vessels form they recruit vascular smooth muscle which stabilises the vessel into a mature and quiescent state. Angiogenesis is induced by signals such as hypoxia inducible factor-1 (HIF1), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGFβ). Mature vessels will shed their vascular smooth muscle coats and endothelial cells will proliferate and migrate to the source of the signals and form new vessels. Thalidomide targets the immature, unstable, newly formed vessels preventing proliferation and migration of the endothelial cells. In rapidly growing tissues, e.g. the forming limb, vessel loss will be devastating, as cell death will be induced and signalling pathways will be disrupted.
