Novel nanocomposite stent coating releasing resveratrol and quercetin reduces neointimal hyperplasia and promotes re-endothelialization

Late-term thrombosis associated with drug-eluting stents may be due to the non-selective actions of antimitogenic drugs on endothelial cells, leading to delayed vascular healing after stenting angioplasty. Currently, there is a need for stent-based therapies that can both attenuate neointimal hyperplasia and promote re-endothelialization. The aim of this study was to compare the effects of a resveratrol (R)- and quercetin (Q)-eluting stent with that of a bare metal stent (BMS) on neointimal hyperplasia and re-endothelialization in a rat model of arterial angioplasty and stenting. Miniature stents (2.5 × 1.25 mm) were sprayed with nanocomposite coatings containing two concentrations of R:Q (50:25 μg/cm2 (RQ1) or 150:75 μg/cm2 (RQ2)). The stents were deployed into the common carotid artery of rats and their impact on vascular remodeling was compared to that of BMS. Luminal stenosis in arteries stented with RQ2-eluting stents was reduced by 64.6% (p < 0.05) compared to arteries stented with BMS. Accompanying this effect was a 59.8% reduction in macrophage infiltration (p < 0.05). There were no differences found between RQ1 and BMS. Finally, the RQ2-coated stent accelerated re-endothelialization by 50% compared with BMS (p < 0.05). Thus, compared with BMS, local delivery of R and Q from a stent platform significantly reduced in-stent stenosis, while promoting re-endothelialization. These data suggest that R and Q may be favorable candidates for novel stent coatings, potentially reducing the risk of late thrombosis associated with drug-eluting stents.

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