Proteasome inhibitor inhibits fibrin Clot retraction, thrombosis and hemostasis.

<p>(A) Platelets were washed and resuspended at 1 × 10⁸/mL in buffer (see “Experimental Procedures”) in the presence of 500 μg/mL human fibrinogen, and fibrin clot was initiated by 0.025 U/mL thrombin at 37°C. Figure represents time frames of a retracting clot at the indicated time points. (B) Clot retraction kinetics curves in the absence or the presence of proteasome inhibitor (MG132). Clot surface areas were assessed by digital processing and plotted as percentage of maximal retraction (<i>i</i>.<i>e</i>. volume of platelet suspension); **P < 0.01, Mann-Whitney test. (C) Mice were injected either 3% Tween 80 (5 mL/kg, vehicle), 6 mg/kg MG132 (**P < 0.01, Mann-Whitney test) or 2.5 mg/kg bortezomib (***P < 0.001, Mann-Whitney test) in 3% Tween 80 by tail vain injection. (D) One hour post-dosing, FeCl₃ induced thrombosis measurements were conducted as described in the “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119363#sec002" target="_blank">Methods</a>” section; **P < 0.01, Mann-Whitney test (for MG132) and ***P < 0.001, Mann-Whitney test (for bortezomib). Each point represents the bleeding time/occlusion time of a single animal (n = 5).