Involvement of Protease Inhibitors in Staphylokinase-Induced Fibrin-Specific Fibrinolysis.

Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential?

T HROMBOTIC COMPLICATIONS of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis, and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic sy...

On the mechanism of fibrin-specific plasminogen activation by staphylokinase.

The mechanism of plasminogen activation by recombinant staphylokinase was studied both in the absence and in the presence of fibrin, in purified systems, and in human plasma. Staphylokinase, like streptokinase, forms a stoichiometric complex with plasminogen that activates plasminogen following Michaelis-Menten kinetics with Km = 7.0 microM and k2 = 1.5 s-1. In purified systems, alpha 2-antipla...

Natural inhibitors of fibrinolysis.

From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease.

HIV protease (PR) represents a prime target for rational drug design, and protease inhibitors (PI) are powerful antiviral drugs. Most of the current PIs are pseudopeptide compounds with limited bioavailability and stability, and their use is compromised by high costs, side effects, and development of resistant strains. In our search for novel PI structures, we have identified a group of inorgan...

Dynamic changes of fibrin architecture during fibrin formation and intrinsic fibrinolysis of fibrin-rich clots.

Clotting and fibrinolysis are initiated simultaneously in vivo, and fibrinolysis usually occurs without any individualized lysis front (intrinsic fibrinolysis). We have developed a novel model to assess whether morphological changes resulting from intrinsic fibrinolysis are similar to those previously reported at the lysis front using externally applied lytic agents. Fibrin assembly and fibrino...