Dysfunctional endothelial-derived microparticles promote inflammatory macrophage formation via NF-кB and IL-1β signal pathways

Yanfang Wang, Jie Liu, Xiaoli Chen, Huimin Sun, Sheng Peng, Yashu Kuang, Jingjiang Pi, Tao Zhuang, Lin Zhang, Zuoren Yu, Brain Tomlinson, Paul Chan, Yihan Chen, Yuzhen Zhang, Ying Li

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16 引文 斯高帕斯(Scopus)


Background: 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. Methods: 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. Results: 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. Conclusion: 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.
頁(從 - 到)476-486
期刊Journal of Cellular and Molecular Medicine
出版狀態已發佈 - 1月 1 2019

ASJC Scopus subject areas

  • 分子醫學
  • 細胞生物學


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