AIM2 regulates vascular smooth muscle cell migration in atherosclerosis

Abstract

BackgroundAtherosclerosis (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. MethodsThe 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. ResultsResults 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 overexpression 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-β/SMAD signaling pathway in VSMCs. ConclusionThus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs.