title: Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study.
abstract: 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.
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jianpang
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Hou
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents / Q000009:adverse effects; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits; D015203:Reproducibility of Results; D015607:Stents / Q000009:adverse effects*; D041623:Tomography, Optical Coherence
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D008727:Methotrexate