Interleukin-35 promotes early endothelialization after stent implantation by regulating macrophage activation.
Clin Sci (Lond)
; 133(7): 869-884, 2019 04 15.
Article
en En
| MEDLINE
| ID: mdl-30914441
ABSTRACT
Background:
Early strut coverage after sirolimus-eluting stent (SES) implantation is associated with the activation of inflammation, but the underlying mechanisms are not completely understood. The present study aimed to identify the relationship between the anti-inflammatory cytokine interleukin (IL) 35 (IL-35) and early strut coverage in vivo and in vitroMethods:
We utilized a retrospective study design to measure IL-35 levels in 68 stents from 68 patients with coronary artery disease and recorded serial optical coherence tomography (OCT) images (0 and 3 months) to assess stent endothelialization. The mechanism underlying the regulatory effects of IL-35 on macrophages and human umbilical vein endothelial cells (HUVECs) was also investigated. SESs were surgically implanted into the right common carotid arteries of 200 male New Zealand White rabbits receiving intravenous injections of IL-35 or a placebo.Results:
At the 3-month OCT evaluation, complete endothelium coverage was correlated with IL-35 levels. IL-35 induced the activation of an anti-inflammatory M2-like macrophage phenotype by targeting the signal transducer and activators of transcription (STAT)1/4 signalling pathway, and IL-35-treated macrophages induced endothelial proliferation and alleviated endothelial dysfunction. IL-35-treated New Zealand White rabbits with implanted SESs showed lower percentages of cross-sections with an uncovered strut, elevated mean neointimal hyperplasia (NIH) thickness, and inhibited inflammatory responses.Conclusions:
We investigated the effect of IL-35 expression on early stent endothelialization in vivo and in vitro and identified a crucial role for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype. The present study highlights a new therapeutic strategy for early stent endothelialization.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de la Arteria Coronaria
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Interleucinas
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Vasos Coronarios
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Células Endoteliales
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Proliferación Celular
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Stents Liberadores de Fármacos
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Intervención Coronaria Percutánea
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Activación de Macrófagos
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Macrófagos
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2019
Tipo del documento:
Article