Figure 1.
Schematic representation of the plasminogen (fibrinolytic) system.
The proenzyme, plasminogen, is converted to the active enzyme plasmin by tissue-type plasminogen activator (t-PA) or by urokinase-type plasminogen activator (u-PA), which binds to a cellular u-PA receptor (u-PAR). Plasmin degrades fibrin and can convert latent matrix metalloproteinases (pro-MMPs) into active MMPs, which in turn degrade extracellular matrix (ECM). Pro-MMPs may also be activated directly by u-PA, or by other MMP. t-PA mediated plasminogen activation is primarily involved in fibrin homeostasis, while plasmin generation via u-PA, complexed with u-PAR plays a role in tissue remodeling. Inhibition may occur at the level of the plasminogen activators by plasminogen activator inhibitors (mainly PAI-1 and possibly PAI-2), at the level of plasmin by α2-antiplasmin and at the level of the MMPs by tissue inhibitors of MMP's (TIMPs).