Abstract
BackgroundThe goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model.MethodsIn vitro proliferation assays were performed using isolated human endothelial and smooth muscle cells to investigate the cell-specific pharmacokinetic effects of CREG and sirolimus. We implanted CREGES, control sirolimus-eluting stents (SES) or bare metal stents (BMS) into pig coronary arteries. Histology and immunohistochemistry were performed to assess the efficacy of CREGES in inhibiting neointimal formation.ResultsCREG and sirolimus inhibited in vitro vascular smooth muscle cell proliferation to a similar degree. Interestingly, human endothelial cell proliferation was only significantly inhibited by sirolimus and was increased by CREG. CREGES attenuated neointimal formation after 4 weeks in porcine coronary model compared with BMS. No differences were found in the injury and inflammation scores among the groups. Scanning electron microscopy and CD31 staining by immunohistochemistry demonstrated an accelerated reendothelialization in the CREGES group compared with the SES or BMS control groups.ConclusionsThe current study suggests that CREGES reduces neointimal formation, promotes reendothelialization in porcine coronary stent model.
Highlights
Multiple studies have shown a remarkable reduction in the rate of restenosis and the need for new revascularization procedures associated with drug-eluting stents (DES) compared with conventional bare metal stents[1,2]
We suggest that a sustained delivery of CREG protein to the vessel wall can be achieved with loaded stents, which could limit neointimal formation in vivo
Elution of the CREG protein from the Stent Wire in Vitro The time-dependent, radioactivity-based measurement demonstrated a biexponential elution of CREG protein from the stent, with an initial rapid washoff followed by a slower exponential reduction in the amount of protein persisting on the stent wires (Figure 2)
Summary
Multiple studies have shown a remarkable reduction in the rate of restenosis and the need for new revascularization procedures associated with drug-eluting stents (DES) compared with conventional bare metal stents[1,2]. The approved drug-eluting stent platforms use a polymer-based coating for the retardation of drug release. There is evidence that the application of polymers may lead to hypersensitivity reactions and, in a few cases, late cardiac death [5,6]. The issue of late-stent thrombosis associated with DES, after discontinuation of antiplatelet therapy, is currently the subject of ongoing discussion. The goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model
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