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.