Abstract
Cardiovascular disorders are among the most widespread pathologies in both industrial and developing countries [1, 2]. An important role in the chemotherapy of cardiovascular disorders belongs to thrombolytic drugs, the administration of which significantly decreases the lethal outcome in patients suffering from myocardial infarction [3, 4]. Effective preparations for thrombolytic therapy are the physiological plasminogen activators representing serine proteases of the tissue (tissue plasminogen activator, t-PA) or urokinase (urokinase, UK; prourokinase, proUK) types and bacterial proteins (streptokinase, Strk; staphylokinase, Stph) acquiring biocatalytic properties upon interaction with plasminogen (Pmg) or plasmin (Pm). These drugs, usually referred to simply as plasminogen activators (PAs), catalyze the hydrolysis of Pmg at the Arg – Val bond with the formation of active Pm. Action of the latter agent leads to degradation of the insoluble fibrin clot which is the reinforcing (framework) basis of thrombi. Characterized by a short lifetime (halflife in the blood stream, 0.1 sec), Pm is effectively inhibited by 2-antiplasmin ( 2-AP) and (to a lesser extent) by 2-macroglobulin ( 2-MG), while the tissue and urokinase PAs in the plasma are inhibited by a plasminogen activator inhibitor of the first type (PAI-1). Fibrin (Fb) serves not only as a substrate for Pm but as a surface for the specific adsorption of Pmg and t-PA as well. Under the action of pulsating pressure in the blood stream, Fb can be saturated with PAs that even do not possess significant affinity with respect to Fb. Fibrinolytic transformations on Fb protect components of the fibrinolytic system from the action of plasma inhibitors and enhance the Pmg activation. This is a general (Fig. 1) scheme of the possible interactions of PAs involved in exogenous thrombolysis. DEVELOPMENT OF NEW EFFECTIVE ACTIVATORS
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