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Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis
Author(s) -
He S.,
Wu C.,
Xiao J.,
Li D.,
Sun Z.,
Li M.
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12648
Subject(s) - proinflammatory cytokine , microbiology and biotechnology , microvesicles , inflammation , klf2 , macrophage , umbilical vein , monocyte , biology , flow cytometry , immunology , chemistry , in vitro , downregulation and upregulation , microrna , biochemistry , gene
Endothelial cells ( EC s) and macrophages engage in tight and specific interactions that play critical roles in cardiovascular homeostasis and the pathogenesis of atherosclerosis. Extracellular vesicles ( EV s) are circular membrane fragments released from the endosomal compartment as exosomes or shed from the surfaces of the membranes of most cell types. Increasing evidence indicates that EV s play a pivotal role in cell‐to‐cell communication. However, the contribution of EV s, as determine by oxidized low‐density lipoprotein (ox‐ LDL )‐exposed and/or Kruppel‐like factor 2 ( KLF 2)‐transduced EC s in the interaction between vascular EC s and monocytes/macrophages, which is a key event in atherosclerotic plaque development, has remained elusive. This study demonstrates the characteristic impact of EV s from ox‐ LDL ‐treated and/or KLF 2‐transduced EC s on the monocyte/macrophage phenotype in vitro and in vivo.Q‐ PCR showed that both the atherosclerosis inducer ox‐ LDL and atheroprotective factor KLF 2 regulated inflammation‐associated micro RNA ‐155 (miR‐155) expression in human umbilical vein endothelial cells ( HUVEC s). Moreover, coculture, immunofluorescence and flow cytometry revealed that miR‐155 was enriched in ox‐ LDL ‐induced EC s‐ EV s and subsequently transferred to human monocytic THP 1 cells, in which these vesicles enhance monocyte activation by shifting the monocytes/macrophages balance from anti‐inflammatory M2 macrophages towards proinflammatory M1 macrophages; EV s from KLF 2‐expressing EC s suppressed monocyte activation by enhancing immunomodulatory responses and diminishing proinflammatory responses, which indicate the potent anti‐inflammatory activities of these cells. Furthermore, oil red staining showed that atherosclerotic lesions were reduced in mice that received EV s from KLF 2‐transduced EC s with decreased proinflammatory M1 macrophages and increased anti‐inflammatory M2 macrophages, and this effect is at least partly due to the decreased expression of inflammation‐associated miR‐155, confirming our in vitro findings. In summary, this study provides novel insights into the pathophysiological effects of altered EV secretion and/or micro RNA content and their influence on modulating monocyte activation depending on the environment surrounding EV s‐releasing EC s.