CELLULAR FIBRINOLYSIS AND ANGIOGENESIS

Angiogenesis is essentially controlled in vascular endothelial cells b y their cellular regulation of the fibrinolytic system. The cell-assoc iated fibrinolytic system is defined as cellular fibrinolysis. The rec eptors (u-PAR, t-PAR and Plg-R) on the cell surface bind their corresp onding ligands (u-PA, t-PA and plasminogen, respectively) acid initiat e local and effective fibrinolytic activity which leads to activated m atrix metalloproteinases. Assembly of these proteinases around the cel ls results in enhanced pericellular proteolysis. These enzymatic activ ities are basically involved in the process of angiogenesis. Various a ngiogenic factors (growth factors, cytokines) regulate the expression of these receptor systems as well as inhibitor systems (PAI-1, TIMPs). Therefore, cellular fibrinolysis on endothelial cells is upregulated in the early stage of angiogenesis for the cells to degrade basement m embrane and migrate through extracellular matrix. Thereafter, the cell ular fibrinolysis is downregulated in the later stage of angiogenesiss for the migrated cells to reorganize and form tubular structures.