ADAMTS13 exerts a thrombolytic effect in microcirculation

• DOI: 10.1160/th12-01-0046
• Publication Date: 2012-07-11T04:35:42Z
• Authors: Melanie Demers; Jaymie R. Voorhees; Siu Wong; Benoit Ho-Tin-Noé; Marilena Crescente; Grace M. Thomas; Denisa D. Wagner
• Keywords: ADAMTS13; Intravital microscopy; Ex vivo; Venule

Summary Recombinant tissue plasminogen activator (r-tPA) is the drug of choice for thrombolysis, but it associated with a significant risk bleeding and not always successful. By cleaving von Willebrand factor (VWF), metalloprotease ADAMTS13 (a disintegrin-like thrombospondin type I repeats-13) down-regulates thrombus formation in injured vessels. We investigated whether recombinant (r-ADAMTS13) induces thrombolysis vivo mice. Thrombosis was produced by ferric chloride-induced (FeCl3) injury venules dorsal skinfold chamber. Phosphate-buffered saline (PBS, vehicle), r-tPA or r-ADAMTS13, supplemented hirudin (to stop ongoing thrombin generation), directly applied onto occluded vessel, dissolution evaluated intravital microscopy. The incidence blood flow restoration significantly increased 30 minutes (min) after r-ADAMTS13 vs. PBS treatment (60% 0%, p<0.05) 60 min (75% 17%, p<0.05). Both reduced size their superfusion (53.2% 62.3% initial size, p<0.05 p<0.01, respectively). Bleeding occurred all r-tPA-treated chambers, while absent mice treated PBS. observed that, similar to r-tPA, can dissolve occlusive thrombi induced FeCl3 venules. In contrast thrombolytic effect any signs haemorrhage. could represent new therapeutic option thrombolysis.