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Facilitation of urokinase‐mediated fibrinolysis by MST‐188 (833.7)
Author(s) -
Fareed Jawed,
Syed Daneyal,
Emanuele Marty,
Hoppensteadt Debra,
Cho Jae
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.833.7
Subject(s) - fibrinolysis , urokinase , fibrin , chemistry , thrombin , lysis , pharmacology , biophysics , biochemistry , immunology , medicine , biology , platelet
Introduction MST‐188 (Mast Therapeutics, San Diego, CA.) is a highly purified form of the , triblock copolymer poloxamer 188. It exhibits potent rheologic properties that result in improved blood flow especially under low shear conditions. Initial observations suggested that endogenous fibrinolysis is facilitated by this agent. In this study we investigate the effect of MST‐188 on urokinase induced fibrinolysis. Materials and Methods A dynamic fibrinokinetic assay was used to assess both the assembly and dissolution of fibrin clots. MST‐188 (0 ‐ 10 mg/ml) was added to citrated human plasma with and without urokinase at a concentrations between 0 ‐ 2,500 U/ml (N=10‐15 donors). Clotting was initiated with the sequential addition of and calcium chloride (0.25 uM) and then thrombin (0.5u/ml). Absorbance was monitored to detect the assembly and dissolution of fibrin. Results Control studies of MST‐188 alone had a dose dependent effect on fibrin assembly as reflected by both the rate of change and peak optical density. Urokinase alone showed no effect on clot formation but a dose dependent increase in clot lysis. Supplementation of MST‐188 to urokinase facilitated its lytic profile in a concentration dependent manner accelerating the time to onset of lysis and reducing the overall AUC for clot dissolution. Discussion These results demonstrate that MST‐ 188 increases urokinase mediated fibrinolysis. The increase in the susceptibility of the formed clot to lysis in the presence of MST‐188 may be due to structural modification of the clot. MST‐188 may bind to fibrin strands, thereby modifying their accessibility to the lytic action of generated plasmin.