AIM2 accelerates the atherosclerotic plaque progressions in ApoE-/- mice
AIM2 accelerates the atherosclerotic plaque progressions in ApoE-/- mice
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AIM2 加速 ApoE-/- 小鼠动脉粥样硬化斑块的进展
DOI：
10.1016/j.bbrc.2018.03.005
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发表时间：
2018-04-06
影响因子：
3.1
通讯作者：
An, Fengshuang
中科院分区：
文献类型：
--
作者：
Pan, Jinyu;Han, Li;An, Fengshuang
牙菌斑的形成是由血管壁中的细胞死亡引发和触发的，这逐渐导致动脉粥样硬化的进展。凋亡是一种新发现的编程细胞死亡形式。黑色素瘤2（AIM2）（HIN-200蛋白质家族的成员）缺乏在激活炎症中起重要作用。然而，迄今为止，AIM2在动脉粥样硬化斑块进展中的作用和机制尚未得到彻底阐明。在载脂蛋白E缺陷型（APOE-/ - ）小鼠中研究了吞噬作用的作用和该作用的机制。在喂食高脂饮食的APOE - / - 小鼠中研究了AIM2过表达和抑制作用。在体外探索了AIM2在血管平滑肌细胞（VSMC）中的特定作用。结果表明，高脂肪饮食会增加AIM2，ICMA-1，GSDMD-N的表达，这可以通过AIM2表达介导。斑块病变区域是lager，具有AIM2过表达。此外，当AIM2过度表达时，TUNEL阳性细胞会增加。随着AIM2的增加，巨噬细胞增强了。体外研究表明，AIM2和GSDMD-N表达以浓度依赖性方式与OX-LDL水平相关。 AIM2表达与NF-KAPPA B信号活性有关，可以被NF-KAPPA B抑制剂抑制。 AIM2通过ASC，Caspasel途径介导GSDMD活性。 ETHD-III和TUNEL染色表明AIM2介导VSMC中的凋亡。我们的研究表明，AIM2不仅是炎性体的常规，而且是动脉粥样硬化的积极参与者。 （c）2018 Elsevier Inc.保留所有权利。
Plaque formation is initiated and triggered by cell death in the vascular wall, which gradually leads to the progression of atherosclerosis. Pyroptosis is a newly discovered form of programmed cell death. Absent in melanoma 2 (AIM2), a member of the HIN-200 protein family, plays an important role in activating inflammasomes. However, the role and mechanism of AIM2 in atherosclerotic plaque progression has not been thoroughly elucidated to date. The effect of pyroptosis and the mechanism for this effect were investigated in apolipoprotein E-deficient (ApoE-/-) mice. AIM2 overexpression and inhibition were studied in ApoE-/- mice that were fed a high-fat diet. The specific role of AIM2 in vascular smooth muscle cells (VSMCs) was explored in vitro. The results showed that high fat diet increases the expression of AIM2, ICMA-1, GSDMD-N, which could be mediated by AIM2 expression. The plaque lesion area is lager with AIM2 overexpression. Moreover, TUNEL-positive cells were increased when AIM2 was over expressed. With increased AIM2, macrophages were enhanced. In vitro studies showed that AIM2 and GSDMD-N expression correlated with ox-LDL levels in a concentration dependent manner. AIM2 expression is associated with NF-kappa B signaling activity and can be inhibited by NF-kappa B inhibitor. AIM2 mediated GSDMD activity through ASC, caspasel pathway. EthD-III and TUNEL staining showed that AIM2 mediates pyroptosis in VSMCs. Our study suggests that AIM2 is not only a regular of inflammasome but also an active participant in atherosclerosis. (C) 2018 Elsevier Inc. All rights reserved.