Macrophage Foam Cell-Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion.
Macrophage Foam Cell-Derived Extracellular Vesicles Promote Vascular Smooth Muscle Cell Migration and Adhesion.
复制标题
巨噬细胞泡沫细胞衍生的细胞外囊泡促进血管平滑肌细胞迁移和粘附。
DOI：
10.1161/jaha.116.004099
复制
发表时间：
2016-10-17
影响因子：
5.4
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Niu C;Wang X;Zhao M;Cai T;Liu P;Li J;Willard B;Zu L;Zhou E;Li Y;Pan B;Yang F;Zheng L
最近出现了一种新的细胞间通讯机制，涉及细胞外囊泡（EV）的细胞间转移。一些研究表明，EV可能在动脉粥样硬化病变中的巨噬细胞泡沫细胞和血管平滑肌细胞（VSMCs）之间的细胞间通讯中发挥潜在作用。这项研究涉及动脉粥样硬化患者和对照参与者的循环EV的比较。结果表明，患者的循环中含有更多的白细胞来源的EV，并且这些EV比健康参与者促进更多的VSMC粘附和迁移。然后，我们建立了巨噬细胞泡沫细胞模型，并表征了来自巨噬细胞的EV。我们使用流式细胞术分析和细胞迁移和粘附测定，并确定泡沫细胞产生的EV比正常巨噬细胞更多，并且泡沫细胞衍生的EV能够促进VSMC迁移和粘附水平的增加。此外，我们对EV进行了蛋白质组学分析。结果表明，泡沫细胞源性EV可能通过调节肌动蛋白细胞骨架和粘着斑途径促进VSMC的粘附和迁移。此外，Western blotting显示泡沫细胞来源的EV可以以时间依赖性方式促进VSMCs中ERK和Akt的磷酸化。我们还发现泡沫细胞来源的EV可以进入VSMC并将整合素转移到这些细胞的表面。本研究的数据首次证明了泡沫细胞中的EV可以促进VSMC的迁移和粘附，这可能是通过EV整合到VSMC中以及随后下游ERK和Akt的激活来介导的。
A new mechanism for intercellular communication has recently emerged that involves intercellular transfer of extracellular vesicles (EVs). Several studies have indicated that EVs may play a potential role in cell‐to‐cell communication between macrophage foam cells and vascular smooth muscle cells (VSMCs) in atherosclerotic lesion. This study involved the comparison of circulating EVs from atherosclerotic patients and control participants. The results showed that the circulation of the patients contained more leukocyte‐derived EVs and that these EVs promoted more VSMC adhesion and migration than those of healthy participants. We then established a macrophage foam cell model and characterized the EVs from the macrophages. We used flow cytometric analyses and cell migration and adhesion assays and determined that the foam cells generated more EVs than the normal macrophages and that the foam cell–derived EVs were capable of promoting increased levels of VSMC migration and adhesion. Furthermore, we performed a proteomic analysis of the EVs. The data showed that the foam cell–derived EVs may promote VSMC adhesion and migration by regulating the actin cytoskeleton and focal adhesion pathways. In addition, Western blotting revealed that foam cell–derived EVs could promote the phosphorylation of ERK and Akt in VSMCs in a time‐dependent manner. We also found that foam cell–derived EVs could enter the VSMCs and transfer integrins to the surface of these cells. The data in our present study provide the first evidence that EVs from foam cells could promote VSMC migration and adhesion, which may be mediated by the integration of EVs into VSMCs and the subsequent downstream activation of ERK and Akt.