AIM2 regulates vascular smooth muscle cell migration in atherosclerosis
AIM2 regulates vascular smooth muscle cell migration in atherosclerosis
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AIM2调节动脉粥样硬化中血管平滑肌细胞迁移
DOI：
10.1016/j.bbrc.2018.02.094
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发表时间：
2018-02-26
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;Lu, Lu;An, Fengshuang
背景：动脉粥样硬化（AS）是各种心脑血管疾病共同的病理基础。斑块的形成是由血管平滑肌细胞（VSMCs）在血管壁的迁移启动和触发的，它逐渐加速动脉粥样硬化的进展。AIM 2是HIN-200家族的成员，在激活炎性小体中起重要作用。然而，AIM 2在炎症小体外动脉粥样硬化斑块进展中的作用尚未报道。方法：在载脂蛋白E缺陷（ApoE-/-）小鼠中研究AIM 2的潜在作用和潜在机制。构建鼠AIM 2慢病毒、shRNA-AIM 2慢病毒和无效慢病毒，并将其静脉内注射到ApoE-/-小鼠中，所述ApoE-/-小鼠以高脂肪饮食喂养。结果：AIM 2过表达的大鼠主动脉粥样硬化病变面积增大，血管平滑肌细胞数量增加，血管平滑肌细胞数量增加。AIM 2的过表达也诱导MMP 2的表达增加。体外研究显示，不同水平的ox-LDL以时间依赖性方式增加AIM 2表达。Transwell结果显示AIM 2介导VSMCs的迁移。ROS抑制剂可抑制AIM 2的表达。此外，AIM 2的过表达和抑制显著影响HG诱导的VSMCs迁移和TGF-β/SMAD信号通路。结论：AIM 2可能通过增加VSMCs的迁移促进动脉粥样硬化斑块的进展。(C)2018爱思唯尔公司All rights reserved.
Background: Atherosclerosis (AS) is a common pathological basis of various cardiovascular and cerebrovascular diseases. Plaque formation is initiated and triggered by vascular smooth musclecells (VSMCs) migration in vascular wall, which gradually aggravates atherosclerosis progression. Absent in melanoma 2 (AIM2), a member of HIN-200 family, plays an important role in activating inflammasome. However, the role of AIM2 in atherosclerotic plaque progression outside of the inflammasome has not yet been reported.Methods: The potential effect and the underlying mechanism of AIM2 were investigated in apoliporotein E-deficient (ApoE-/-) mice. Murine AIM2 lentivirus, shRNA-AIM2 lentivirus and null lentivirus were constructed and injected intravenously into ApoE-/- mice, which were fed on a high fat diet. The specific mechanism of AIM2 in vascular smooth cells (VSMCs) was explored in vitro.Results: Results showed the aortic atherosclerotic lesion area was larger with AIM2 over-expression, and the number of smooth muscle cells was enhanced in line with the increased AIM2 levels. AIM2 over expression also induced the increasing expression of MMP2. In vitro studies revealed that different levels of ox-LDL increased AIM2 expression in a time dependent manner. Transwell showed that AIM2 mediated migration in VSMCs. The expression of AIM2 can be inhibited when the ROS inhibitor was used. Additionally, the overexpression and inhibition of AIM2 significantly affects HG-induced migration and TGF-beta/SMAD signaling pathway in VSMCs.Conclusion: Thus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs. (C) 2018 Elsevier Inc. All rights reserved.