Andrianova K. In vitro modelling design for studying some stages of fibrinolytic process

The influence of fibrin clot microenvironment on it's structure and fibrinolysis was investigated. For this purpose the dynamic model of studying the fibrinolysis process under flow condition was designed. In one experimental setting, fibrin surface is degraded with enzymes applied in the recirculating fluid phase; in another setting, clots containing gel-embedded plasmin(ogen) are washed with enzyme-free buffer. Our results suggested that the essential role of fibrin clot degradation played gel-embedded plasmin(ogen). It was found, that either a2-macroglobulin or fibrin degradation products didn't affect on the rate of fibrinolysis. Oxyacids, instead, strongly influenced on fibrin clot structure and inhibited the rate of its lysis. But in vivo the micellar clot structure, which was formed at the presence of oxyacids, still hasn't shown. The essential influence on speed of fibrin degradation by the elastase-digested products of plasminogen was indicated. Angiostatins, kringles 1-3 and 4 containing fragments of a heavy chain, decrease rate of fibrin clot lysis only after reaching threshold level of concentration in 500 nM, while the dependence of miniplasminogen concentration on the rate of fibrinolysis was linear. The inhibition effect of miniplasminogen appeared to be consisting of two factors. About 60% belonged to kringle 5, which overlapped sites of primary interaction of Glu-plasminogen with fibrin. The rest - to the competition of SP-domain of miniplasminogen with plasminogen for the tissue activator.