Endogenously Generated Plasmin at the Vascular Wall Injury Site Amplifies Lysine Binding Site-Dependent Plasminogen Accumulation in Microthrombi
Fig 6
tPA-induced lysis of microthrombi.
(A) tPA was injected at a dose of 3 mg/kg 40 minutes after the laser-induced injury. Images were captured 2 minutes before and every 5 minutes up to one hour after tPA administration. (B) In another set of experiments, EACA (4.25 mmol/kg) was administered intravenously through the femoral vein of GFP-mice 10 minutes before the laser injury, and images were captured in a similar manner. In both Figures (A) and (B), the upper panel shows horizontal plane (X-Y) images and the lower panel shows perpendicular plane (Y-Z) images, which were reconstructed from sequential optical sections of microthrombi. Arrows show the direction of blood flow. The scale bars represent 10 μm. (C) Relative changes in the volumes of thrombi after tPA administration. tPA or saline was injected at time 0 (arrow). Volumes of thrombi were normalized to their values 2 minutes before saline or tPA injection. Thrombi in mice treated with saline did not change in size (gray squares), whereas all of the thrombi in mice treated with tPA 40 minutes after the laser injury dissolved completely within 35 minutes after tPA administration (white squares). When mice were pretreated with EACA 10 minutes before the laser injury, however, tPA-dependent thrombolysis was totally inhibited (black squares). Each point represents the mean value of 5 thrombi from 5 mice ± SD.