Macrophage-derived foam cells impair endothelial barrier function by inducing endothelial-mesenchymal transition via CCL-4.
Macrophage-derived foam cells impair endothelial barrier function by inducing endothelial-mesenchymal transition via CCL-4.
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巨噬细胞衍生的泡沫细胞通过 CCL-4 诱导内皮-间质转化损害内皮屏障功能
DOI：
10.3892/ijmm.2017.3034
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发表时间：
2017-08
影响因子：
5.4
通讯作者：
Chen YX
中科院分区：
文献类型：
--
作者：
Yang Y;Luo NS;Ying R;Xie Y;Chen JY;Wang XQ;Gu ZJ;Mai JT;Liu WH;Wu MX;Chen ZT;Fang YB;Zhang HF;Zuo ZY;Wang JF;Chen YX
近来，内皮-间充质转化（EndMT）已被证实在动脉粥样硬化的发生发展中发挥重要作用，但其分子机制仍不明确。在本研究中，扫描电子显微镜直接显示内皮间隙增宽，免疫荧光检测表明人主动脉粥样硬化斑块中EndMT增加。M1型巨噬细胞衍生的泡沫细胞（M1 - FC）培养上清液可诱导EndMT，而M2型巨噬细胞衍生的泡沫细胞（M2 - FC）培养上清液则无此作用。蛋白质芯片和酶联免疫吸附试验鉴定出，在可促进EndMT的M1 - FC培养上清液中，包括C - C基序趋化因子配体4（CCL - 4）在内的几种细胞因子水平升高，同时伴有内皮通透性增加和单核细胞黏附增多。此外，抗CCL - 4抗体可消除M1 - FC培养上清液对EndMT的影响。与此同时，CCL - 4激活其受体C - C基序趋化因子受体 - 5（CCR - 5），并上调转化生长因子 - β（TGF - β）的表达。进一步实验表明，CCR - 5拮抗剂处理以及RNA介导的TGF - β基因敲低可逆转CCL - 4诱导的EndMT。总体而言，本研究数据表明，M1 - FC通过上调CCL - 4诱导EndMT，并增加内皮通透性和单核细胞黏附。这些数据可能有助于阐明EndMT在动脉粥样硬化发生发展中的重要作用。
Recently, endothelial-mesenchymal transition (EndMT) has been demonstrated to play an important role in the development of atherosclerosis, the molecular mechanisms of which remain unclear. In the present study, scanning electron microscopy directly revealed a widened endothelial space and immunohistofluorescence demonstrated that EndMT was increased in human aorta atherosclerotic plaques. M1 macrophage-derived foam cell (M1-FC) supernatants, but not M2 macrophage-derived foam cell (M2-FC) supernatants, induced EndMT. A protein array and enzyme-linked immunosorbent assay identified that the levels of several cytokines, including C-C motif chemokine ligand 4 (CCL-4) were increased in M1-FC supernatants, in which EndMT was promoted, accompanied by increased endothelial permeability and monocyte adhesion. Furthermore, anti-CCL-4 antibody abolished the effects of M1-FC supernatants on EndMT. At the same time, CCL-4 activated its receptor, C-C motif chemokine receptor-5 (CCR-5), and upregulated transforming growth factor-β (TGF-β) expression. Further experiments revealed that EndMT induced by CCL-4 was reversed by treatment with CCR-5 antagonist and the RNA-mediated knockdown of TGF-β. On the whole, the data of the present study suggest that M1-FCs induce EndMT by upregulating CCL-4, and increase endothelial permeability and monocyte adhesion. These data may help to elucidate the important role of EndMT in the development of atherosclerosis.
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影响因子：
11.5
作者：
Choi, Seo-Hyun;Hong, Zhen-Yu;Lee, Yoon-Jin
通讯作者：
Lee, Yoon-Jin
DOI：
10.1161/atvbaha.115.305438
发表时间：
2015-05-01
影响因子：
8.7
作者：
McAlpine, Cameron S.;Huang, Aric;Werstuck, Geoff H.
通讯作者：
Werstuck, Geoff H.
影响因子：
8.1
作者：
Kim M;Neinast MD;Frank AP;Sun K;Park J;Zehr JA;Vishvanath L;Morselli E;Amelotte M;Palmer BF;Gupta RK;Scherer PE;Clegg DJ
通讯作者：
Clegg DJ
DOI：
10.1161/atvbaha.116.308014
发表时间：
2016-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Herbin O;Regelmann AG;Ramkhelawon B;Weinstein EG;Moore KJ;Alexandropoulos K
通讯作者：
Alexandropoulos K
影响因子：
3.5
作者：
Hung, YC;Hong, MY;Huang, GS
通讯作者：
Huang, GS