期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 510, 期 4, 页码 565-572出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.02.005
关键词
Exosome; Atherosclerosis; microRNA; Macrophage; Mesenchymalstem cells; Polarization
资金
- National Natural Science Foundation of China [81571284, 91542115, 81702468, 81874083, 81802966]
- National Natural Science Foundation of Shandong Province of China [2017CXGC1203 2017G006012, 2013GGE27006]
- Taishan Scholars of Shandong Province of China [ts201511093]
Atherosclerosis is a chronic inflammatory disease of the vasculature. Exosomes derived from mesenchymal stem cells (MSCs) exert immunomodulatory and immunosuppressive effects; however, the MSCs-exosomes administration on atherosclerosis was unknown. Here, our ApoE(-/-) mice were fed a high-fat diet and received intravenous injections of exosomes from MSCs for 12 weeks. After tail-vein injection, MSCs-exosomes were capable of migrating to atherosclerotic plaque and selectively taking up residence near macrophages. MSCs-exosomes treatment decreased the atherosclerotic plaque area of ApoE(-/-) mice and greatly reduced the infiltration of macrophages in the plaque, associating induced macrophage polarization towards M2. In vitro, MSCs-exosomes treatment markedly inhibited LPS-induced M1 markers expression, while increased M2 markers expression in macrophages. Moreover, miR-let7 family was found to be highly enriched in MSCs-exosomes. Endogenous miR-let7 expression was found in the aortic root of ApoE(-/-) mice, and MSCs-exosomes treatment further up-regulated miR-let7 levels. In addition, inhibition of miR-let7 in 1.1937 cells significantly inhibited the migration and M2 polarization via IGF2BP1 and HMGA2 pathway respectively in vitro. Our study demonstrates that MSC-sexosomes ameliorated atherosclerosis in ApoE(-/-) and promoted M2 macrophage polarization in the plaque through miR-let7/HMGA2/NF-kappa B pathway. In addition, MSCs-exosomes suppressed macrophage infiltration via miR-let7/IGF2BP1/PTEN pathway in the plaque. This finding extends our knowledge on MSCs-exosomes affect inflammation in atherosclerosis plaque and provides a potential method to prevent the atherosclerosis. Exosomes from MSCs hold promise as therapeutic agents to reduce the residual risk of coronary artery diseases. (C) 2019 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据