ABSTRACT
In the simplest sense, angiogenesis is the process by which perfusion pathway length and vessel segment number are increased within a vascular bed. In normal situations, this effective increase in vessel density delivers more blood to the tissue facilitating tissue growth and/or increased tissue activity (i.e. endocrine production and release) (Ferrara, 1999; Risau, 1997). Consequently, angiogenesis is a primary component of tissue vascularization such as occurs during development (Breier et al., 1997), following an upstream occlusive event leading to tissue ischemia (Couffinhal et al., 1998) or during proliferative events as seen in tissue repair (Carmeliet and Collen, 1997; Thakral et al., 1979), and tumors (Folkman and Cotran, 1976). It is generally believed that interactions between vascular cells and tissue cells, primarily through paracrine activities, play an important role in the initiation and regulation of angiogenesis within a tissue (Furcht, 1986). However, considerable detail is lacking in our understanding of the angiogenesis process and vascularization as a whole. Although we know many of the factors and signals that initiate or terminate the vascularization process, it is not clear at all how new vessel segments form while maintaining a semblance to a blood vessel and progress into a functional vessel segment within a larger, vascular bed. Clearly angiogenesis is integrated with other vascularization processes such as arteriogenesis (Schaper and Buschmann, 1999), vascular remodeling (Gibbons and Dzau, 1994), adaptation (Pries and Secomb, 2000a; Skalak et al., 1998), and vascular polarization (Holder and Klein, 1999) to establish a vasculature. However, the basis for this integration and the mechanisms driving vascularization are not known.
