Fibrinolysis in a lipid environment: modulation through release of free fatty acids.

BACKGROUND: Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, but the structure of clots in vivo includes additional constituents (proteins, phospholipids) that modulate their solubilization. OBJECTIVE: We examined the presence of free fatty acids in thrombi and their effects on distinct stages of fibrinolysis (plasminogen activation, plasmin activity). METHODS AND RESULTS: Using the fluorescent probe acrylodated intestinal fatty acid-binding protein, variable quantities (up to millimolar concentrations) of free fatty acids were demonstrated in surgically removed human thrombi. Oleic acid at relevant concentrations reversibly inhibits more than 90% of the amidolytic activity of plasmin on a synthetic substrate (Spectrozyme PL), but only partially inhibits its fibrinolytic activity measured using turbidimetry. Chromogenic assays detecting the generated plasmin activity show that plasminogen activation by tissue-type plasminogen activator (t-PA) is completely blocked by oleic acid in the fluid phase, but is accelerated on a fibrin matrix. A recombinant derivative of t-PA (reteplase) develops higher fibrin specificity in the presence of oleic acid, because both the inhibition of plasminogen activation in free solution and its enhancement on fibrin template are stronger than with wild-type t-PA. CONCLUSION: Through the stimulation of plasminogen activation on a fibrin template and the inhibition of plasminogen activators and plasmin in the fluid phase, free fatty acids confine the action of fibrinolytic proteases to the site of clotting, where they partially oppose the thrombolytic barrier function of phospholipids.

Reversible adsorption-desorption oscillations of nanoparticles on a patterned hydrogel surface induced by a pH oscillator in a closed chemical system.

Oscillatory adsorption-desorption of Ag nanoparticles on a pH-responsive hydrogel surface was induced by a pH oscillator in a closed reaction system. The hydrogel surface was prepared as a honeycomb-patterned film using a honeycomb-patterned polystyrene film as a template to speed up the response time in the stimuli-responsive hydrogel. The surface morphology and hydrophobic interaction of the patterned hydrogel surface were significantly altered by the pH change of the aqueous solution that came into contact with the gel. The surface of the hydrogel became hydrophobic for adsorption in a lower-pH solution but became hydrophilic with decreased adsorptivity at higher pH conditions. A closed system chemical pH oscillator composed of CaSO3-H2O2-NaHCO3-H2SO4 was applied to force the periodic adsorption-desorption of Ag nanoparticles on the gel surface. The experimental conditions for the chemical oscillator were optimized to obtain long-lasting high-amplitude pH oscillations in a closed reactor. The periodic adsorption-desorption was proved to be induced by the periodic pH change in the solution, although the two phenomena were not completely synchronized. That is, the periodic time was longer and the number of oscillations was less for the adsorption-desorption compared with the pH oscillations that occurred in the solution state. However, the heterogeneous oscillations obtained in this study clearly suggested that the hydrophobic interaction was reversibly changed in the patterned pH-responsive hydrogel surface, similar to various biological systems in nature.