Angiogenesis: a dynamic balance of stimulators and inhibitors

Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, is tightly regulated in normal adults. Under physiological circumstances, angiogenesis occurs in only a few instances; e.g., the female reproductive system in response to ovulation or gestation, the normal hair cycle, etc. In these examples, growth of new capillaries is tightly controlled by an interplay of growth regulatory proteins which act either to stimulate or to inhibit blood vessel growth. Normally, the balance between these forces is tipped in favor of inhibition and consequently capillary growth is restrained. Under certain pathological circumstances, however, local inhibitory controls are unable to restrain the increased activity of angiogenic inducers. Thus, in wound healing, inflammation and tumors, to name just a few examples, angiogenesis is integral to the pathology, engendering the hope that these pathological entities could be regulated by pharmacological and/or genetic suppression (or enhancement) of blood vessel growth. This hope, in turn, has fostered interest in the molecular mechanisms that regulate angiogenesis. In this chapter, we have reviewed the current literature regarding some angiogenic stimulators and inhibitors, emphasizing vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), as a major angiogenic inducer, and thrombospondin (TSP) as the best known example of a natural inhibitor of vessel growth.