Statin Therapybefore Percutaneous Coronary Intervention:A Novel Bridge between Thrombin and Thrombomodulin for Enhanced CardiovascularProtection

Percutaneous coronary intervention administration of statins enhances the thrombin–thrombomodulin (TM) interaction, which is critical for the prevention of post-procedural cardiovascular complications. Atomic force microscopy showed that statins increased the single molecule rupture forces between thrombin and TM, suggesting a strengthened complex. This was supported by surface plasmon resonance, which showed an enhanced binding affinity under the statin treatment. Molecular docking and dynamics simulations revealed that statins can bind to both thrombin and TM, forming stable complexes that facilitate protein C activation. Clinically relevant doses of statins were found to significantly enhance the thrombin–TM interaction, potentially reducing the risk of myocardial infarction and stent thrombosis by augmenting the endothelial anticoagulant properties through the thrombin–TM pathway. By acting as a bridge, statins foster more stable thrombin–TM complexes, supporting endogenous anticoagulant mechanisms and leading to better cardiovascular outcomes.