title: Novel nanocomposite stent coating releasing resveratrol and quercetin reduces neointimal hyperplasia and promotes re-endothelialization.
abstract: 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 (2.5×1.25mm) were sprayed with nanocomposite coatings containing two concentrations of R:Q (50:25μg/cm(2) (RQ1) or 150:75μg/cm(2) (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.
authors.affiliation: Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71103, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kleinedler
authors.forename: John D
authors.initials: JD
authors.lastname: Foley
authors.forename: Elysse A
authors.initials: EA
authors.lastname: Orchard
authors.forename: Tammy R
authors.initials: TR
authors.lastname: Dugas
mesh_terms: D017130:Angioplasty; D000818:Animals; D050256:Antimitotic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D003251:Constriction, Pathologic / Q000188:drug therapy; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006965:Hyperplasia / Q000188:drug therapy / Q000473:pathology; D008297:Male; D053761:Nanocomposites; D058426:Neointima / Q000188:drug therapy / Q000473:pathology; D011794:Quercetin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D050256:Antimitotic Agents; D013267:Stilbenes; D011794:Quercetin; D000077185:Resveratrol