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  • Title: Polycations selectively blocking tissue factor-dependent FVII activation: collective in vitro anticoagulation studies.
    Author: Chu AJ.
    Journal: Inflamm Allergy Drug Targets; 2011 Feb; 10(1):13-8. PubMed ID: 21184651.
    Abstract:
    Tissue factor (TF) is an initiator of the extrinsic blood coagulation, which is often susceptible to upregulation by tissue injury, advanced glycation end-product, or diverse inflammation. TF hypercoagulability is accompanied by elevated generation of clotting factors (e.g., FVIIa, FXa, and thrombin) and fibrin production, all of which are proinflammatory. In this laboratory, our in vitro experimental results show that polycationic anticoagulants (compound 48/80, ruthenium red, polybrene, protamine, Buforin I, and cationic polyamino acids) intervene TF hypercoagulability at posttranslational level. Polycations preferentially suppress TF-dependent FVII activation with diminished FVIIa formation shown on Western blotting, resulting in non- or un-competitive inhibition on FVIIa amidolytic activity. In contrast, polycations have no effect on FVIIa catalysis, FXa activity, or thrombin activity per se. Polycations could present a new class of anticoagulants with such unique upstream downregulation of blood coagulation. In view of coagulation-dependent inflammation and the new paradigm of blood coagulation-inflammation-thrombosis circuit, the polycations as a new class of anticoagulants could effectively contribute to antiinflammation, antithrombosis, and cardioprotection. Further development of effective anticoagulants is of biopharmaceutical significance in broadly easing disease conditions.
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