Angiogenesis

Blood vessels are required to supply oxygen and nutrients and to remove waste products from tissue. In the healthy adult organism, angiogenesis (the formation of new blood vessels) is a rare event that occurs in wound healing and for a few days each month in the female reproductive tract. In contrast to developmental angiogenesis, stress-induced angiogenesis is largely independent of anatomical boundaries, but rather occurs in a refined area of hypoxia or tissue damage. The genetic program directing this form of neovascularization is part of the stress response and is overlapping with, but distinct from the genetic program that directs blood vessel formation in morphogenesis during embryonic development. After wounding, platelets produce chemotactic factors, including TGF-β and PDGF. These factors activate fibroblasts to produce MMPs and growth factors, which degrade the extracellular matrix, stimulate the infiltration by macrophages, and promote blood vessel formation. The production of MMPs, UPA, and TPA facilitates the reepithelialization of the wound. Repair is also reflected in the secretion of the Fibroblast Growth Factors -1 and -2, Interleukin-8, and Osteopontin, as well as in the expression of the Integrins α_νβ₃ and α_νβ₅, and possibly α₁β₁ and α₂β₁, on endothelial cells during angiogenesis, but not prominently on endothelial cells within mature blood vessels. The blood vessel formation in neoplasms is akin to wound healing [Dvorak 1984] or inflammation.