FRONTIERS IN CARDIOVASCULAR PHYSIOLOGY Fibrinolysis

Abstract

Fibrinolysis is essentially performed by plasmin, the activity of which is regulated by balanced (regulatory) systems. The key factors in these intricate blood plasma systems have been identified as tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1), both of which are produced by the vascular wall and removed from the circulation by the liver. The properties of t-PA and PAI-1 and identified processes that may be responsible for their activity are described. t-PA and PAI-1 bind to the vascular endothelium, which implies that the nonthrombogenic character of the vascular wall is also determined by the presence of both factors. Observations in vitro suggest that multiple surface-related processes act as thrombosis-preventing systems by inactivating PAI-1 and thrombin. The levels of t-PA and PAI-1 expression are subject to modulation in vitro by endogenous substances that preferentially affect t-PA (eg, vitamin A) or PAI-1 (eg, cytokines). Correlation of these findings with observations in vivo have been reported. Biochemical analysis elucidated that this modulation is at the level of gene regulation. Based on recent experimental data it is concluded that blood fibrinolytic activity is a reflection of the balanced synthesis of fibrinolytic key factors by the vessel wall and that cell surface-related processes determine the nonthrombogenic character of the vascular endothelium.