Proliferation of blood vessels is a process necessary for the nonnal growth and development of tissue (36). In the adult, angiogenesis occurs infrequently. Exceptions are found in the female reproductive system, where angiogenesis occurs in the follicle during its development, in the corpus luteum during ovulation, and in the placenta after pregnancy. These periods of angiogenesis are relatively brief and tightly regulated. Nonnal angiogenesis also occurs as part of the body's repair processes, e.g. in the healing of wounds and fractures. By contrast, uncontrolled angiogenesis can often be pathological. For example, the growth of solid tumors depends on vascularization (37), and in diabetic retinopathy vascularization of the retina often leads to blindness. Given the physiologic and pathological importance of angiogenesis, much effort in the last twenty years has been devoted to the isolation, characteriza tion, and purification of factors that can either stimulate or inhibit an giogenesis. Several bioassays have been developed to measure angiogenesis. The most common ones are endothelial cell migration (47) and proliferation (38) in vitro, and capillary growth in vivo in the developing chick chorioallantoic membrane (CAM) (4) and the cornea (45). The goal of this review is to describe those stimulators and inhibitors of angiogenesis that have been best-characterized.
Klagsbrun et al. (1991) studied this question.