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Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study

This study used optical coherence tomography (OCT) to investigate the effects of systemic methotrexate, in combination with a drug-eluting stent, on in-stent neoatherosclerosis in a rabbit model. Sirolimus-eluting stents were surgically implanted in the right common carotid arteries of 200 male New...

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Autores principales: Zhang, Ruoxi, Chen, Shuyuan, Zhang, Hui, Liu, Qi, Xing, Jianpang, Zhao, Qi, Wang, Yu, Yu, Bo, Hou, Jingbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028880/
https://www.ncbi.nlm.nih.gov/pubmed/27644847
http://dx.doi.org/10.1038/srep33657
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author Zhang, Ruoxi
Chen, Shuyuan
Zhang, Hui
Liu, Qi
Xing, Jianpang
Zhao, Qi
Wang, Yu
Yu, Bo
Hou, Jingbo
author_facet Zhang, Ruoxi
Chen, Shuyuan
Zhang, Hui
Liu, Qi
Xing, Jianpang
Zhao, Qi
Wang, Yu
Yu, Bo
Hou, Jingbo
author_sort Zhang, Ruoxi
collection PubMed
description This study used optical coherence tomography (OCT) to investigate the effects of systemic methotrexate, in combination with a drug-eluting stent, on in-stent neoatherosclerosis in a rabbit model. Sirolimus-eluting stents were surgically implanted in the right common carotid arteries of 200 male New Zealand White rabbits; the animals received a high-fat diet, beginning one week before stent implantation. Each animal was randomly assigned to 1 of 4 groups, receiving intravenous injections of either methotrexate (0.4 mg/kg) or placebo weekly for 4 or 12 weeks. Stented arterial segments were harvested after stenting for 4 or 12 weeks, and processed for OCT and histological analysis. Prior to harvesting the arterial segments, blood was collected for the determinations of cytokine levels. Compared with the control animals, the methotrexate-treated animals showed lower rates of lipid-rich intima and per-strut low-signal intensity layers, smaller neointimal areas, and reduced neointimal thickness; larger fibrous cap thicknesses and smaller lumen areas were also seen in the animals receiving methotrexate. The levels of serum interleukin, adhesion molecules, and nuclear factor-κB p65 decreased and IL-10 level increased in the methotrexate-treated animals. Targeting the pro-inflammatory pathways may be an effective way to prevent restenosis without the long-term risk of late thrombosis.
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spelling pubmed-50288802016-09-26 Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study Zhang, Ruoxi Chen, Shuyuan Zhang, Hui Liu, Qi Xing, Jianpang Zhao, Qi Wang, Yu Yu, Bo Hou, Jingbo Sci Rep Article This study used optical coherence tomography (OCT) to investigate the effects of systemic methotrexate, in combination with a drug-eluting stent, on in-stent neoatherosclerosis in a rabbit model. Sirolimus-eluting stents were surgically implanted in the right common carotid arteries of 200 male New Zealand White rabbits; the animals received a high-fat diet, beginning one week before stent implantation. Each animal was randomly assigned to 1 of 4 groups, receiving intravenous injections of either methotrexate (0.4 mg/kg) or placebo weekly for 4 or 12 weeks. Stented arterial segments were harvested after stenting for 4 or 12 weeks, and processed for OCT and histological analysis. Prior to harvesting the arterial segments, blood was collected for the determinations of cytokine levels. Compared with the control animals, the methotrexate-treated animals showed lower rates of lipid-rich intima and per-strut low-signal intensity layers, smaller neointimal areas, and reduced neointimal thickness; larger fibrous cap thicknesses and smaller lumen areas were also seen in the animals receiving methotrexate. The levels of serum interleukin, adhesion molecules, and nuclear factor-κB p65 decreased and IL-10 level increased in the methotrexate-treated animals. Targeting the pro-inflammatory pathways may be an effective way to prevent restenosis without the long-term risk of late thrombosis. Nature Publishing Group 2016-09-20 /pmc/articles/PMC5028880/ /pubmed/27644847 http://dx.doi.org/10.1038/srep33657 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Ruoxi
Chen, Shuyuan
Zhang, Hui
Liu, Qi
Xing, Jianpang
Zhao, Qi
Wang, Yu
Yu, Bo
Hou, Jingbo
Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
title Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
title_full Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
title_fullStr Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
title_full_unstemmed Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
title_short Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
title_sort effects of methotrexate in a rabbit model of in-stent neoatherosclerosis: an optical coherence tomography study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028880/
https://www.ncbi.nlm.nih.gov/pubmed/27644847
http://dx.doi.org/10.1038/srep33657
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