Antithrombotic Effect of a Bivalent DNA Aptamer of Thrombin.

Thrombin plays a critical role in both coagulation and platelet activation, and its interaction with thrombin-protease-activated receptor 1 (PAR1) on platelets and vascular smooth muscle cells (VSMCs) leads to a series of pathological processes such as thrombosis, restenosis, and atherosclerosis. This study investigated the antithrombotic properties of a bivalent DNA aptamer (bApt) with phosphorothioate backbone modification designed to inhibit thrombin, with a specific focus on its ability to regulate the thrombin-PAR1 signaling pathway. The results showed that bApt modulated the thrombin-PAR1 pathway, effectively reduced thrombus formation, platelet aggregation, and VSMC proliferation. Key findings from the study highlight that bApt successfully prolonged coagulation reaction time (R value), coagulation time (K value), maximum amplitude (MA) and reduced coagulation angle (α value), and also prolonged thrombin time (TT) and activated partial thromboplastin time (APTT), in a dose-dependent manner. Moreover, in an arterial injury model, bApt reduced thrombus formation significantly, supporting its potential as a therapeutic agent for thrombotic diseases.