Exosomal MALAT1 derived from oxidized low-density lipoprotein-treated endothelial cells promotes M2 macrophage polarization

Huang,Chaoyang; Han,Jie; Wu,Yutao; Li,Shan; Wang,Qiwen; Lin ,Wenjuan; Zhu,Jianhua

doi:10.3892/mmr.2018.8982

Exosomal MALAT1 derived from oxidized low-density lipoprotein-treated endothelial cells promotes M2 macrophage polarization

Authors:
- Chaoyang Huang
- Jie Han
- Yutao Wu
- Shan Li
- Qiwen Wang
- Wenjuan Lin
- Jianhua Zhu
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China
Published online on: May 7, 2018 https://doi.org/10.3892/mmr.2018.8982
Pages: 509-515

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Abstract

Oxidized low-density lipoprotein (oxLDL)-induced injury and apoptosis of endothelial cells are important initial events in numerous cardiovascular diseases. Following activation by oxLDL, monocytes adhere to endothelial cells, migrate into the subendothelial spaces and then undergo differentiation into macrophages, which subsequently induces the formation of atherosclerotic lesions. However, the mechanisms underlying the activation of macrophage differentiation by oxLDL-treated endothelial cells remain unclear. In the present study, it was demonstrated that exosomal metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was increased in oxLDL-treated human umbilical vein endothelial cells. When co-cultured with monocytes, exosomes extracted from oxLDL-treated HUVECs were endocytosed. Furthermore, exosomes derived from oxLDL-treated endothelial cells were revealed to promote M2 macrophage polarization, as reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA analyses demonstrated increases in the expression of M2 macrophage markers, including macrophage mannose receptor 1 (also termed CD206), arginase-1 and interleukin (IL)-10, and decreases in the expression of the M1 macrophage marker, IL-12. Furthermore, the suppression of MALAT1 expression in monocytes was demonstrated to reverse exosome-mediated M2 macrophage polarization. In conclusion, the results of the present study revealed a novel mechanism underlying the onset of atherogenesis associated with endothelial cells and macrophages: Exosomal MALAT1 derived from oxLDL-treated endothelial cells promoted M2 macrophage polarization. This result may provide a novel scientific basis for the understanding of atherosclerosis progression.

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