Angiogenesis.

Abstract

Regulation of Angiogenesis in Health and DiseaseAngiogenesis is a fundamental process by which new blood vessels are formed (1).It is essential in reproduction, development, and wound repair.Under these conditions, angiogenesis is highly regulated, i.e. turned on for brief periods (days) and then completely inhibited.However, many diseases are driven by persistent unregulated angiogenesis.In arthritis, new capillary blood vessels invade the joint and destroy cartilage.In diabetes, new capillaries in the retina invade the vitreous, bleed, and cause blindness (2).Ocular neovascularization is the most common cause of blindness and dominates approximately 20-eye diseases.Tumor growth and metastasis are angiogenesis-dependent (3, 4).A tumor must continuously stimulate the growth of new capillary blood vessels for the tumor itself to grow.Furthermore, the new blood vessels embedded in a tumor provide a gateway for tumor cells to enter the circulation and to metastasize to distant sites, such as liver, lung, or bone.Capillary blood vessels consist of endothelial cells and pericytes.These two cell types carry all of the genetic information to form tubes, branches, and whole capillary networks.Specific angiogenic molecules can initiate this process.Specific inhibitory molecules can stop it.These molecules with opposing functions appear to be continuously acting in concert to maintain a quiescent microvasculature in which endothelial cell turnover is thousands of days.However, the same endothelial cells can undergo rapid proliferation (5-day turnover) during spurts of angiogenesis, for example in wound healing.The proteins which regulate the coagulation system and the family of proteins which regulate the hematopoietic system, including the colony-stimulating factors, interleukins and erythropoietin ( 5 ) , appear to operate by a similar program.The protein interactions of these latter systems, however, are better understood than are the proteins involved in angiogenesis.Angiogenic factors and inhibitors have been discovered only in the past decade, and while their properties can be listed (Table I), the elucidation of their interactions with each other is only beginning to be uncovered.The same can be said of non-vascular cells, such as macrophages and mast cells, which may modulate the angiogenic response. Angiogenic Molecules