Stents eluting 6-mercaptopurine reduce neointima formation and inflammation while enhancing strut coverage in rabbits

Matthijs S. Ruiter, Claudia M. Van Tiel, Albert Doornbos, Goran Marinković, Aart C. Strang, Nico J M Attevelt, Vivian De Waard, Robbert J. De Winter, Rob Steendam, Carlie J M De Vries

Research output: Contribution to journalArticlepeer-review

Abstract

Background The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface. Methods Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions. Results Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation. Conclusion We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6- MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.

Original languageEnglish
Article number138459
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 21 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Fingerprint

Dive into the research topics of 'Stents eluting 6-mercaptopurine reduce neointima formation and inflammation while enhancing strut coverage in rabbits'. Together they form a unique fingerprint.

Cite this