title: Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model.
abstract: OBJECTIVE
  The use of currently marketed drug-eluting stents presents safety concerns including increased late thrombosis, which is thought to result mainly from delayed endothelial healing effects (impaired re-endothelialization resulting in abnormal inflammation and fibrin deposition). We recently developed a bioabsorbable polymeric nanoparticle (NP)-eluting stent using a novel cationic electrodeposition technology. Statins are known to inhibit the proliferation of vascular smooth muscle cells (VSMC) and to promote vascular healing. We therefore hypothesized that statin-incorporated NP-eluting stents would attenuate in-stent stenosis without delayed endothelial healing effects.
  
  
  METHODS
  Among six marketed statins, pitavastatin (Pitava) was found to have the most potent effects on VSMC proliferation and endothelial regeneration in vitro. We thus formulated a Pitava-NP-eluting stent (20µg Pitava per stent).
  
  
  RESULTS
  In a pig coronary artery model, Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as polymer-coated sirolimus-eluting stents (SES). At SES sites, delayed endothelial healing effects were noted, whereas no such effects were observed in Pitava-NP-eluting stent sites.
  
  
  CONCLUSIONS
  Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as SES without the delayed endothelial healing effects of SES in a porcine coronary artery model. This nanotechnology platform could be developed into a safer and more effective device in the future.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tsukie
authors.forename: Kaku
authors.initials: K
authors.lastname: Nakano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matoba
authors.forename: Seigo
authors.initials: S
authors.lastname: Masuda
authors.forename: Eiko
authors.initials: E
authors.lastname: Iwata
authors.forename: Miho
authors.initials: M
authors.lastname: Miyagawa
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Junji
authors.initials: J
authors.lastname: Kishimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D011804:Quinolines / Q000008:administration & dosage*; D013552:Swine
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; C108475:pitavastatin