ANGIOGENESIS - A PARADIGM FOR BALANCED EXTRACELLULAR PROTEOLYSIS DURING CELL-MIGRATION AND MORPHOGENESIS

Extracellular proteolysis is required for matrix degradation and the r egulation of cytokine activity during angiogenesis, and this is depend ent on a cohort of proteases and protease inhibitors produced by endot helial and nonendothelial cells. The plasminogen activator (PA)/plasmi n system has been extensively investigated in these processes, and des criptive studies have demonstrated that urokinase-type PA(uPA), uPA re ceptor (uPAR) and PA inhibitor-1 (PAI-1) are expressed by endothelial cells during angiogenesis in vivo. In vitro studies have led to the na tion that normal capillary morphogenesis is dependent on a protease-an tiprotease equilibrium. These findings are discussed in the context of recent observations on uPA-, uPAR-, PAI-1 and plaminogen-deficient mi ce, in which developmental and physiological angiogenesis appear to oc cur normally. This has led to a reevaluation of the role of the PA/pla smin system during angiogenesis. In particular, these observations rai se the possibility that the role of this system may be limited to situ ations in which endothelial cells encounter and must degrade fibrin in order to form new capillary sprouts.