The Angiopoietins: Yin and Yang in Angiogenesis

Embryonic vascular development involves a complex series of events during which endothelial cells differentiate, proliferate, migrate, and undergo morphological organization in the context of their surrounding tissues (Risau 1991, 1995). Vascular development is generally classified into two successive phases. The first, known as vasculogenesis, refers to the process whereby newly differentiated endothelial cells spontaneously coassemble into tubules that fuse to form a rather homogeneous primary vasculature in the embryo. Subsequent remodeling of this primary vascular network into large and small vessels brings into play a different process, termed angiogenesis. Angiogenesis in the embryo also leads to the sprouting of vessels into certain initially avascular organs, such as the brain. In the adult, angiogenesis accounts for neovascularization that accompanies the normal remodeling of the female reproductive organs during the menstrual cycle and pregnancy, in wound healing, and in various clinically significant pathological processes, such as tumor growth and diabetic retinopathy (Folkman 1995; Ferrara 1995; Hanahan and Folkman 1996).