Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE-/- mice
Insulin resistance adipocyte-derived exosomes aggravate atherosclerosis by increasing vasa vasorum angiogenesis in diabetic ApoE-/- mice
复制标题
胰岛素抵抗脂肪细胞来源的外泌体通过增加糖尿病 ApoE(-/-) 小鼠的血管生成来加重动脉粥样硬化
DOI：
10.1016/j.ijcard.2018.04.028
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发表时间：
2018-08-15
影响因子：
3.5
通讯作者：
Zhong, Ming
中科院分区：
文献类型：
--
作者：
Wang, Feng;Chen, Fang-fang;Zhong, Ming
背景：2型糖尿病（T2DM）患者血管新生增加，并可能促进动脉粥样硬化斑块破裂。我们试图确定是否胰岛素抵抗脂肪细胞来源的外泌体（IRADEs）发挥了重要作用，在调制VV血管生成和所涉及的mechanism.Methods：IRADEs的表征进行了电子显微镜，NTA（纳米粒子跟踪分析）和蛋白质印迹。在体外培养的人脐静脉内皮细胞（HUVECs）和小鼠主动脉内皮细胞（MAECs）中研究IRADEs对血管生成的细胞效应。结果：IRADEs在体外呈杯状，可被HUVECs和粥样斑块摄取，并可通过shh促进管腔形成。在主动脉环和基质胶塞试验中，血管生成在IRADE组中显著增加。外源性施用含SHH的IRADEs增加VV血管生成，斑块负荷，脆弱性指数和血管生成相关因子的表达，而这些影响被减弱沉默SHH在IRADEs.Conclusions：总之，IRADEs促进斑块负荷和斑块脆弱性部分通过诱导VV血管生成，这部分通过SHH发生。因此，IRADE的应用可能成为治疗糖尿病动脉粥样硬化的一种新的治疗方法。(c)2018爱思唯尔B.V.保留所有权利。
Background: Vasa vasorum (VV) angiogenesis is increased in type 2 diabetes mellitus (T2DM) and may promote atherosclerotic plaque rupture. We sought to determine whether insulin resistance adipocyte-derived exosomes (IRADEs) played a major role in modulating VV angiogenesis and the mechanisms involved.Methods: The characterization of IRADEs was performed by electron microscopy, NTA (Nanoparticle Tracking Analysis) and western blot. The cellular effects of IRADEs on angiogenesis were explored in human umbilical vein endothelial cells (HUVECs) and murine aortic endothelial cells (MAECs) in vitro. The roles of IRADEs in angiogenesis were demonstrated with aortic ring and matrigel plug assays ex vivo and the plaque burden, plaque stability and angiogenesis-related protein expression in vivo were evaluated by ultrasonography, immunohistochemistry and western blot.Results: The IRADEs had a cup-shaped morphology, could be taken up by HUVECs and atherosclerotic plaques, and promoted tube formation by shh in vitro. In the aortic ring and matrigel plug assays, angiogenesis was significantly increased in the IRADEs group. Exogenously administered shh-containing IRADEs increased VV angiogenesis, the plaque burden, the vulnerability index and the expression of angiogenesis-related factors, whereas these effects were attenuated by silencing shh in IRADEs.Conclusions: In conclusion, IRADEs promote plaque burden and plaque vulnerability partly by inducing VV angiogenesis, which occurs partly through shh. Accordingly, the application of IRADEs may serve as a novel therapeutic approach to treat diabetic atherosclerosis. (c) 2018 Elsevier B.V. All rights reserved.