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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

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

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.

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0 (Coated Materials, Biocompatible)
0 (Immunosuppressive Agents)
0 (Polymers)
E7WED276I5 (Mercaptopurine)

Date Created: 20150922 Date Completed: 20160531 Latest Revision: 20220316

20240829

PMC4577071

10.1371/journal.pone.0138459

26389595