Despite its function as an inhibitor of urokinase and tissue-type plasminogen activator (PA), PA inhibitor-1 (PAI-1) has a paradoxical protumorigenic role in cancer, promoting angiogenesis and tumor cell survival. In this review, we summarize preclinical evidence in support of the protumorigenic function of PAI-1 that has led to the testing of small-molecule PAI-1 inhibitors, initially develope...

The interactions between exogenously added tissue-type plasminogen activator (t-PA) and the active form of type 1 plasminogen activator inhibitor (PAI-1) produced by and present in cultured human umbilical vein endothelial cells (HUVECs) were investigated. Immunoblotting analysis of the conditioned media obtained from monolayers of HUVECs treated with increasing concentrations of t-PA (less tha...

Tissue-type plasminogen activator (t-PA) is less active in vivo and in vitro against clots that are enriched in platelets, even at therapeutic concentrations. The release of radioactivity from ‘El-fibrin-labeled clots was decreased by 47% 6 hours after the addition of t-PA 400 U/mL when formed in plateletrich versus platelet-poor plasma. This difference was not due to the release of plasminogen...

AIM To investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor (VEGF) expressions. METHODS A total of 36 vitreous samples were collected from 36 patients with PDR (PDR group), and 17 vitreous samples from 17 patients w...

We investigated the effects of hemodynamic force on fibrinolytic activity of cultured human umbilical vein endothelial cells stimulated by cytokines, using a modified cone-plate viscometer in which well-controlled and -defined shear forces were generated. Treatment of the cells with interleukin (IL)-beta or tumor necrosis factor alpha (TNFalpha) under static conditions had no effect on tissue p...

In recent years, the role and physiological regulation of the serine protease tissue-type plasminogen activator (t-PA) and its inhibitors, including plasminogen activator inhibitor type-1 (PAI-1), in the brain have received much attention. However, as studies focusing these issues are difficult to perform in humans, a great majority of the studies conducted to date have utilized rodent in vivo ...

For a period of 6 weeks, 76 healthy male volunteers consumed during their daily main meal the contents of one tin (approximately 135 g) of either fish (mackerel) paste or meat paste. Fibrinolytic parameters were determined in plasma samples obtained at the beginning and at the end of the experimental period. No changes were found in plasminogen, alpha 2-antiplasmin, tissue-type plasminogen acti...

We review laboratory tests that evaluate thrombogenesis during acute coronary syndromes. These tests have been found to be valuable research tools in more clearly understanding the pathophysiology of acute coronary syndromes. In particular, we describe tissue factor, tissue factor pathway inhibitor, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrinopeptide A, tissue plasminogen ac...

We compared urokinase-type plasminogen activator (u-PA) in fluid phase and u-PA bound with its receptor on human blood monocytes with respect to proteolytic activity and susceptibility to inactivation by the plasminogen activator inhibitors PAl-i and PAI-2. Receptor-bound u-PA is catalytically twice as efficient as fluid-phase u-PA. Fluidphase u-PA is susceptible to rapid inhibition by PAl-i an...

Previous studies have shown that overall fibrinolytic activity in blood follows a diurnal rhythm with a peak in the morning and a trough in the evening. The purpose of this study was to determine which fibrinolytic factor(s) was responsible for this diurnal rhythm. Resting and postvenous occlusion tissue-type plasminogen activator (t-PA) activity, resting t-PA antigen, and resting plasminogen a...