Jinyu Pan1, Lu Lu2, Xuyang Wang1, Dian Liu1, Jingjing Tian1, Hui Liu1, Mingjun Zhang1, Fengqin Xu2, Fengshuang An3. 1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, No, 107 WenHuaXi Road, Jinan, Shandong, CN 250012, China. 2. Jinan No. 4 People's Hospital, No, 50, Shifan Road, Jinan, Shandong, CN 250031, China. 3. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, No, 107 WenHuaXi Road, Jinan, Shandong, CN 250012, China. Electronic address: fengshuang.an@hotmail.com.
Abstract
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 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. CONCLUSION: Thus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs.
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. MurineAIM2 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 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. CONCLUSION: Thus, we demonstrated that AIM2 could promote the progression of atherosclerotic plaque by increasing migration in VSMCs.
Authors: Lars Brodowski; Tristan Zindler; Sandra von Hardenberg; Bianca Schröder-Heurich; Constantin S von Kaisenberg; Helge Frieling; Carl A Hubel; Thilo Dörk; Frauke von Versen-Höynck Journal: Front Cell Dev Biol Date: 2019-03-19
Authors: Enzo Lüsebrink; Philip Roger Goody; Catharina Lahrmann; Anna Flender; Sven Thomas Niepmann; Andreas Zietzer; Christian Schulz; Steffen Massberg; Felix Jansen; Georg Nickenig; Sebastian Zimmer; Alexander Otto Krogmann Journal: Front Cardiovasc Med Date: 2020-11-11