Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model

J Atheroscler Thromb. 2013;20(1):32-45. doi: 10.5551/jat.13862. Epub 2012 Sep 13.

Abstract

Aim: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • Constriction, Pathologic
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / physiopathology*
  • Disease Models, Animal
  • Drug-Eluting Stents*
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Microscopy, Electron, Scanning
  • Nanoparticles*
  • Quinolines / administration & dosage*
  • Swine

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • pitavastatin