Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits.

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 10 Issue 9 Pg. e0138459 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26389595 (Publication Type: Journal Article)

Chemical References

• Coated Materials, Biocompatible
• Immunosuppressive Agents
• Polymers
• Mercaptopurine

Topics

• Animals
• Coated Materials, Biocompatible (chemistry)
• Drug-Eluting Stents (adverse effects)
• Iliac Artery (drug effects, pathology, surgery)
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Inflammation (etiology, immunology, pathology, prevention & control)
• Male
• Mercaptopurine (administration & dosage, therapeutic use)
• Neointima (etiology, immunology, pathology, prevention & control)
• Polymers (chemistry)
• Rabbits