Fibroblast growth factors as angiogenesis factors: New insights into their mechanism of action

Angiogenesis is critical for physiological processes such as embryonic development and wound repair (D’Amore and Thompson, 1987; Folkman and Shing, 1992). Angiogenesis also contributes to several pathologies either directly, as in diabetic retinopathy, or indirectly by supporting the growth of pathological tissues, as in rheumatoid arthritis and tumor growth (Folkman, 1995). During angiogenesis, new capillaries arise as sprouts from preexisting capillaries or post-capillary venules. This phenomenon is accomplished by a series of sequential steps. In the initial phase of capillary sprouting, the basement membrane of endothelial cells in the parent blood vessel is degraded. Degradation of the basement membrane is mediated by endothelial cell proteinases, most notably plasminogen activators (PAs) and a variety of matrix-degrading metalloproteinases (MMPs). Once the basement membrane is degraded, endothelial cells bud out from the preexisting vessel and migrate into the perivascular space. Cells at the base of the sprout proliferate and replace migrated cells. Initially, the tubes or cords contain no lumen; a new basement membrane is formed, and after two contiguous sprouts have fused to form a loop, a lumen forms and blood begins to flow (Ausprunk and Folkman, 1977).