Angiogenesis: An Introduction*
*Part of this chapter has
been published in:
Liekens, S., De Clercq, E. and Neyts, J.
"Angiogenesis: regulators and clinical applications"
Biochem. Pharmacol. 61:253-270 (2001).
Vascular endothelial cells cover the entire inner surface of blood vessels in the body. Growth of the vascular system is primarily a developmental process, which occurs during embryogenesis and only to a limited extent in postnatal life.
Two processes are responsible for the formation of new blood vessels: vasculogenesis and angiogenesis.
Early during embryogenesis,
blood islands composed of progenitor cells of blood cells (hematopoietic
cells) and endothelial cells (angioblasts) differentiate from the mesoderm.
The formation of blood vessels from differentiating angioblasts and their
organization into a primordial vascular network, consisting of the major
blood vessels of the embryo, is called vasculogenesis
|Angiogenesis involves the formation of vascular sprouts from pre-existing vessels, resulting in a highly branched vascular plexus. This primary capillary plexus is remodeled several times until a mature vascular system consisting of vessels of different diameters and functions is formed. While vasculogenesis is limited to early embryogenesis, angiogenesis occurs both during development and in postnatal life (198).|
Angiogenesis is a fundamental process in reproduction (107) and wound healing. Under these conditions angiogenesis is highly regulated, i.e. turned on for a short period and then completely inhibited. Unregulated angiogenesis may result in different pathologies (75). In arthritis, new capillaries invade the joint and destroy cartilage (133). Ocular neovascularization, which is often associated with diabetes, is the most common cause of blindness (67). Furthermore, uncontrolled angiogenesis may lead to psoriasis and juvenile hemangiomas, strongly vascularized lesions in which the number of newly formed vessels greatly exceeds the metabolic demand of the tissue concerned (187). Finally, tumorgrowth and metastasis are angiogenesis-dependent (98). A growing tumor needs an extensive network of capillaries to provide nutrients and oxygen. In addition, the new intratumoral blood vessels provide a way for tumor cells to enter the circulation and to metastasize to distant organs. Thus, every organ system may involve diseases in which angiogenesis is an important component.