A potential role for mast cells in the release of bFGF from normal myocytes during angiogenesis in vivo

Basic fibroblast growth factor (bFGF) is a potent angiogenic factor produced by cells of mesodermal and neuroectodermal origin. Despite numerous advances, the precise mechanism of bFGF release from cells still remains unknown. Upon release from cells, the protein is stored and protected in the extracellular matrix by binding to heparan sulfate proteoglycans. A number of reports suggest that degrading enzymes secreted by mast cells may play a role in the release of bFGF from connective tissue stores. Additionally, mast cells are believed to play a role in the formation of new blood vessels. In this report, we studied the events involved in neovascularization using a well-characterized model of angiogenesis in rabbits where neovascularization is induced by transfer of a well-perfused rectus abdominis muscle flap to an ischemic limb. Using this model, we demonstrate that bFGF expression is induced in normal myofibers and bFGF is released in the wound fluid at the ischemic/nonischemic interface. The highest concentrations of bFGF were detected on days 14 and 21 postoperation. We also show that the number of mast cells and their degranulation correlate with the release of bFGF from adjacent muscle tissue and the appearance of the growth factor in the wound fluid. There appears to exist a temporal correlation between number of mast cells, their degranulation, and the release of bFGF during angiogenesis in vivo.