Statin Therapy before Percutaneous Coronary Intervention: A Novel Bridge between Thrombin and Thrombomodulin for Enhanced Cardiovascular Protection
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.
Authors
- Bin Lai
- Zhen Wang (ORCID: https://orcid.org/0000-0001-5613-9317)
- Yujie Wei (ORCID: https://orcid.org/0000-0002-3213-7891)
- Xiaohong Fang (ORCID: https://orcid.org/0000-0002-2018-0542)
- Xiaochen Wang (ORCID: https://orcid.org/0000-0003-2901-2075)
- Xiaofeng Wang (ORCID: https://orcid.org/0000-0002-0042-6285)
- Xiaoli Shi (ORCID: https://orcid.org/0000-0003-0866-1164)
Institutions
- North China Electric Power University (CN)
- Anhui Medical University (CN)
- Chinese Academy of Sciences (CN)
- Center for NanoScience (DE)
- Chinese PLA General Hospital (CN)
- Beijing National Laboratory for Molecular Sciences (CN)
- Kansai Electric Power Hospital (JP)
- Institute of High Energy Physics (CN)
- National Center for Nanoscience and Technology (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
- Institute of Chemistry (CN)
- Molecular Sciences Institute (US)
- Center for Excellence in Education (US)
Publication Details
- Journal
- ACS Omega
- Published
- 2025-02-07
- DOI
- https://doi.org/10.1021/acsomega.4c10348
- Primary Topic
- Atrial Fibrillation Management and Outcomes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China