期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 24, 期 24, 页码 14257-14269出版社
WILEY
DOI: 10.1111/jcmm.16043
关键词
platelets; protein disulphide isomerase; tannic acid; thrombosis
资金
- Translational Research Grants of NCRCH [2020ZKPA01]
- National Natural Science Foundation of China [81620108001, 81670134, 81870325, 81900140, 82070450]
- Young Investigator Pre-Research Foundation of the Second Affiliated Hospital of Soochow University [SDFEYQN1717]
- Natural Science Foundation of Jiangsu Province [BK20190819]
- Jiangsu Provincial Key Medical Center
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- NIGMS [P41-GM103311]
Protein disulphide isomerase (PDI) promotes platelet activation and constitutes a novel antithrombotic target. In this study, we reported that a PDI-binding plant polyphenol, tannic acid (TA), inhibits PDI activity, platelet activation and thrombus formation. Molecular docking using plant polyphenols from dietary sources with cardiovascular benefits revealed TA as the most potent binding molecule with PDI active centre. Surface plasmon resonance demonstrated that TA bound PDI with high affinity. Using Di-eosin-glutathione disulphide fluorescence assay and PDI assay kit, we showed that TA inhibited PDI activity. In isolated platelets, TA inhibited platelet aggregation stimulated by either GPVI or ITAM pathway agonists. Flow cytometry showed that TA inhibited thrombin- or CRP-stimulated platelet activation, as reflected by reduced granule secretion and integrin activation. TA also reduced platelet spreading on immobilized fibrinogen and platelet adhesion under flow conditions. In a laser-induced vascular injury mouse model, intraperitoneal injection of TA significantly decreased the size of cremaster arteriole thrombi. No prolongation of mouse jugular vein and tail-bleeding time was observed after TA administration. Therefore, we identified TA from natural polyphenols as a novel inhibitor of PDI function. TA inhibits platelet activation and thrombus formation, suggesting it as a potential antithrombotic agent.
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