Interleukin-35 promotes early endothelialization after stent implantation by regulating macrophage activation

被引:17
|
作者
Liu, Xianglan [1 ,2 ]
Zhang, Ruoxi [1 ,2 ]
Hou, Jingbo [1 ,2 ]
Wu, Jian [1 ,2 ]
Zhang, Maomao [1 ,2 ]
Fang, Shaohong [2 ]
Wang, Xuedong [1 ,2 ]
Huang, Xingtao [1 ,2 ]
Tian, Jinwei [1 ,2 ]
Li, Hulun [2 ]
Sun, Yong [1 ,2 ]
Yu, Bo [1 ,2 ]
机构
[1] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin 150086, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Key Lab Myocardial Ischemia, Minist Educ, Harbin 150086, Heilongjiang, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金; 国家重点研发计划;
关键词
OPTICAL COHERENCE TOMOGRAPHY; SIROLIMUS-ELUTING STENT; NEOINTIMAL COVERAGE; THROMBOSIS; IMPACT; MODEL;
D O I
10.1042/CS20180879
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 vitro. Methods: 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.
引用
收藏
页码:869 / 884
页数:16
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