Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-кB and IL-1β signal pathways.
Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-кB and IL-1β signal pathways.
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功能失调的内皮衍生微粒通过 NF-kB 和 IL-1 β 信号通路促进炎症巨噬细胞形成
DOI：
10.1111/jcmm.13950
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发表时间：
2019-01
影响因子：
5.3
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang Y;Liu J;Chen X;Sun H;Peng S;Kuang Y;Pi J;Zhuang T;Zhang L;Yu Z;Tomlinson B;Chan P;Chen Y;Zhang Y;Li Y
据报道，急性冠脉综合征（ACS）患者循环内皮源性微粒（EMPs）升高。然而，目前尚不清楚来自功能失调的内皮细胞的emp是否参与ACS的发生和进展，以及潜在的机制是什么。测定22例ACS患者和20例无冠状动脉疾病的对照组患者的血浆EMPs。我们将功能失调的人脐静脉内皮细胞（HUVECs）在血清饥饿或缺氧胁迫下产生的emp与健康的HUVECs产生的emp进行了比较。使用共聚焦显微镜和荧光显微镜观察EMPs与单核细胞的结合和NF‐кB的易位。分别用PKH26红色荧光标记、Ki67免疫染色和Sudan IV染色检测氧化低密度脂蛋白的摄取，检测单核细胞粘附、细胞增殖和吞噬作用。与对照组相比，ACS患者的血浆EMPs显著升高。与对照相比，来自应激HUVECs的EMPs产生了更多的促炎细胞因子，这依赖于NF‐кB和IL‐1β信号通路。来自功能失调内皮的EMPs通过NF‐кB和IL‐1β介导的MCP‐1和CCR‐5信号促进单核细胞粘附，并通过NF‐кB和IL‐1β介导的Cyclin D1信号促进增殖。最后，来自功能失调的内皮的emp显示出更大的促进巨噬细胞吞噬形成泡沫细胞产生更多的促炎细胞因子。MPs可能通过NF - κB和IL - 1β依赖性信号参与ACS患者的炎症过程。靶向EMP介导的炎症反应可能是一种有希望的治疗策略，以限制ACS的疾病进展。
Circulating endothelial‐derived microparticles (EMPs) are reported to be increased in acute coronary syndrome (ACS). However, it remains unclear whether EMPs from dysfunctional endothelium participate in the initiation and progression of ACS and what the underlying mechanisms might be. Plasma EMPs were measured in 22 patients with ACS and 20 control patients without coronary artery diseases. EMPs from dysfunctional human umbilical vein endothelial cells (HUVECs) stressed by serum‐starvation or hypoxia were compared to the EMPs from healthy HUVECs. Confocal and fluorescent microscopy was used to visualize the incorporation of EMPs into monocytes and the translocation of NF‐кB. Monocyte adhesion, cell proliferation, and phagocytosis were detected by PKH26 red fluorescent labelling, Ki67 immunostaining, and Sudan IV staining for uptake of oxidized low‐density lipoprotein, respectively. Plasma EMPs was significantly increased in ACS patients compared to controls. EMPs were incorporated into monocytes and EMPs from stressed HUVECs produced more pro‐inflammatory cytokines compared to vehicle control, which was depended on NF‐кB and IL‐1β signal pathways. EMPs from dysfunctional endothelium promoted monocyte adherence via NF‐кB and IL‐1β‐mediated MCP‐1 and CCR‐5 signals, as well as proliferation via the NF‐кB and IL‐1β‐mediated Cyclin D1 signals. Finally, EMPs from dysfunctional endothelium showed greater promotion of macrophage phagocytosis forming foam cells to produce more pro‐inflammatory cytokines. MPs might be involved in the inflammatory process in patients with ACS via NF‐κB and IL‐1β‐dependent signals. Targeting EMP‐mediated inflammatory responses may be a promising therapeutic strategy to limit the progression of disease in ACS.
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影响因子：
3.7
作者：
Rios FJ;Ferracini M;Pecenin M;Koga MM;Wang Y;Ketelhuth DF;Jancar S
通讯作者：
Jancar S
影响因子：
6.7
作者：
Radecke CE;Warrick AE;Singh GD;Rogers JH;Simon SI;Armstrong EJ
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影响因子：
8.7
作者：
Rougerie P;Miskolci V;Cox D
通讯作者：
Cox D
DOI：
10.1161/atvbaha.110.218123
发表时间：
2011-01-01
影响因子：
8.7
作者：
Dignat-George, Francoise;Boulanger, Chantal M.
通讯作者：
Boulanger, Chantal M.
影响因子：
39.3
作者：
Porto, Italo;Biasucci, Luigi Marzio;Crea, Filippo
通讯作者：
Crea, Filippo