Antithrombin Perfluorocarbon Nanoparticle Deposition Prevents Stent Thrombosis
TL;DRAbstract
Background Despite pharmacologic modification of vascular implants, stent thrombosis remains clinically significant. The purpose of this research was to demonstrate the utility of antithrombin nanoparticles to prevent stent thrombosis. Methods: Perfluorocarbon nanoparticles conjugated to multiple copies of the direct thrombin inhibitor D‐phenylalanyl‐L‐prolyl‐L‐arginyl‐chloromethyl ketone (PPACK‐NP) were tested in static and in flow‐loop in vitro models for their ability to prevent thrombosis on bare metal stents. Thrombin‐adsorbed stents were treated with saline, free PPACK, control NP or PPACK‐NP, followed by exposure to platelet poor plasma (PPP) or platelet rich plasma (PRP) for 60 minutes. In PRP‐exposed groups, subsets were pretreated with either clopidogrel or vorapaxar. Results: Treatment of thrombin‐adsorbed stents with PPACK‐NP abrogated clot formation following PPP (p<0.05) or PRP (p<0.0005) exposure. Scanning electron microscopy of PRP exposed stents treated with PPAC
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Background Despite pharmacologic modification of vascular implants, stent thrombosis remains clinically significant. The purpose of this research was to demonstrate the utility of antithrombin nanoparticles to prevent stent thrombosis. Methods: Perfluorocarbon nanoparticles conjugated to multiple copies of the direct thrombin inhibitor D‐phenylalanyl‐L‐prolyl‐L‐arginyl‐chloromethyl ketone (PPACK‐NP) were tested in static and in flow‐loop in vitro models for their ability to prevent thrombosis on bare metal stents. Thrombin‐adsorbed stents were treated with saline, free PPACK, control NP or PPACK‐NP, followed by exposure to platelet poor plasma (PPP) or platelet rich plasma (PRP) for 60 minutes. In PRP‐exposed groups, subsets were pretreated with either clopidogrel or vorapaxar. Results: Treatment of thrombin‐adsorbed stents with PPACK‐NP abrogated clot formation following PPP (p<0.05) or PRP (p<0.0005) exposure. Scanning electron microscopy of PRP exposed stents treated with PPAC
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