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

Noriaki Tsukie, Kaku Nakano, Tetsuya Matoba, Seigo Masuda, Eiko Iwata, Miho Miyagawa, Gang Zhao, Wei Meng, Junji Kishimoto, Kenji Sunagawa, Kensuke Egashira

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 NPeluting 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 (20 μg 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.

Original languageEnglish
Pages (from-to)32-45
Number of pages14
JournalJournal of Atherosclerosis and Thrombosis
Volume20
Issue number1
DOIs
Publication statusPublished - Feb 4 2013

Fingerprint

Stents
Nanoparticles
Coronary Vessels
Pathologic Constriction
Swine
Sirolimus
Hydroxymethylglutaryl-CoA Reductase Inhibitors
pitavastatin
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Electroplating
Nanotechnology
Drug-Eluting Stents
Cell proliferation
Fibrin
Electrodeposition
Blood Vessels
Regeneration

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

Cite this

Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model. / Tsukie, Noriaki; Nakano, Kaku; Matoba, Tetsuya; Masuda, Seigo; Iwata, Eiko; Miyagawa, Miho; Zhao, Gang; Meng, Wei; Kishimoto, Junji; Sunagawa, Kenji; Egashira, Kensuke.

In: Journal of Atherosclerosis and Thrombosis, Vol. 20, No. 1, 04.02.2013, p. 32-45.

Research output: Contribution to journalArticle

@article{2c74dc986b124baeaf36927b1b4c771e,
title = "Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model",
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 NPeluting 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 (20 μg 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.",
author = "Noriaki Tsukie and Kaku Nakano and Tetsuya Matoba and Seigo Masuda and Eiko Iwata and Miho Miyagawa and Gang Zhao and Wei Meng and Junji Kishimoto and Kenji Sunagawa and Kensuke Egashira",
year = "2013",
month = "2",
day = "4",
doi = "10.5551/jat.13862",
language = "English",
volume = "20",
pages = "32--45",
journal = "Journal of Atherosclerosis and Thrombosis",
issn = "1340-3478",
publisher = "Japan Atherosclerosis Society",
number = "1",

}

TY - JOUR

T1 - Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model

AU - Tsukie, Noriaki

AU - Nakano, Kaku

AU - Matoba, Tetsuya

AU - Masuda, Seigo

AU - Iwata, Eiko

AU - Miyagawa, Miho

AU - Zhao, Gang

AU - Meng, Wei

AU - Kishimoto, Junji

AU - Sunagawa, Kenji

AU - Egashira, Kensuke

PY - 2013/2/4

Y1 - 2013/2/4

N2 - 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 NPeluting 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 (20 μg 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.

AB - 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 NPeluting 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 (20 μg 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.

UR - http://www.scopus.com/inward/record.url?scp=84873861122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873861122&partnerID=8YFLogxK

U2 - 10.5551/jat.13862

DO - 10.5551/jat.13862

M3 - Article

C2 - 22986515

AN - SCOPUS:84873861122

VL - 20

SP - 32

EP - 45

JO - Journal of Atherosclerosis and Thrombosis

JF - Journal of Atherosclerosis and Thrombosis

SN - 1340-3478

IS - 1

ER -