Gene targeting and gene transfer studies of the plasminogen/plasmin system: implications in thrombosis, hemostasis,...

The plasminogen/plasmin or fibrinolytic system with its physiological triggers, tissue-type plasminogen activator, and urokinase-type plasminogen activator has been presumed to participate in normal and pathological processes of the vessel wall such as blood clot dissolution (thrombolysis), hemostasis, aneurysm formation, neovascularization, restenosis, and atherosclerosis. The implied role of the fibrinolytic system in vivo is, however, deduced from correlations between fibrinolytic activity and (patho)physiological phenomena, which does not allow establishing a cause/consequence relationship. Gene targeting and gene transfer technologies allow establishment of the in vivo role of gene products more conclusively. This article reviews briefly the findings of such studies on thrombolysis/thrombosis, hemostasis, neointima formation, atherosclerosis, and associated effects on survival.