Glomerular plasminogen activator inhibitor-1 (PAI-1) steady-state mRNA and bioactivity were increased after the induction of an augmented form of antiglomerular basement membrane (GBM) antibody glomerulonephritis. PAI-1 mRNA expression was noted at 6 h, peaking at 1 day, and although falling thereafter, remained higher than that of the control group through Day 17. PAI-1 mRNA expression correla...

Urokinase (u-PA)-mediated cell surface plasminogen activation is required for cellular tissue invasion. This invasion occurs in environments rich in plasminogen activator inhibitors (PAIs), which efficiently inhibit receptor-bound two-chain u-PA. Single-chain u-PA (scu-PA) was recently found to efficiently initiate cell surface plasminogen activation, and we herein describe the interaction of s...

In eighty-three patients with confirmed deep vein thrombosis, the fibrinolytic system was studied before and after a 10-minute venous occlusion. Blood was collected at least 3 months after the last acute episode, and PAI-1 antigen and activity, as well as tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and fibrinolytic activity were measure...

Platelet-rich thrombi are resistant to lysis by tissue-type plasminogen activator (t-PA). Although platelet alpha-granules contain plasminogen activator inhibitor-1 (PAI-1), a fast-acting inhibitor of t-PA, the contribution of PAI-1 to the antifibrinolytic effect of platelets has remained a subject of controversy. We recently reported a patient with a homozygous mutation within the PAI-1 gene t...

Proteolytic joint destruction in inflammatory and non-inflammatory arthropathy is believed to be mediated, at least in part, by the plasminogen activation (PA) system. To further investigate possible involvement of the PA system, we quantified immunoreactive urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), both plasminogen activator inhibitors (PAI-1 and PA...

A computer simulation was developed to study the regulation of active tissue plasminogen activator (t-PA) levels in plasma by kinetically modeling t-PA secretion, t-PA inhibition by plasminogen activator inhibitor type 1 (PAI-1), and hepatic clearance of t-PA, PAI-1 and t-PA/PAI-1 complex throughout a simplified human circulatory system. The model indicates that as the active PAI-1 concentratio...

Generation of the broad spectrum protease plasmin is facilitated by the tissue (t-PA) and urokinase (u-PA) plasminogen activators, within multiple physiological and disease states. Finely tuned control of this proteolytic cascade is exerted by the plasminogen activator inhibitors type-1 (PAI-1/SERPINE1) and 2 (PAI-2/SERPINB2). Expression of this network of activators and inhibitors by cells of ...

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...

AIMS The aim of the study was to test if pharmacological intervention by valproic acid (VPA) treatment can modulate the fibrinolytic system in man, by means of increased acute release capacity of tissue plasminogen activator (t-PA) as well as an altered t-PA/Plasminogen activator inhibitor -1 (PAI-1) balance. Recent data from in vitro research demonstrate that the fibrinolytic system is epigene...