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Oncotarget. 2016 Jun 14;7(24):35562-35576. doi: 10.18632/oncotarget.9384.

Aldehyde dehydrogenase 2 inhibits inflammatory response and regulates atherosclerotic plaque.

Pan C1,2,3,4, Xing JH1,2,3,4, Zhang C2,5, Zhang YM6, Zhang LT1,2,3,4, Wei SJ1,2,3,4, Zhang MX2, Wang XP2, Yuan QH1,2,3,4, Xue L1,2,3,4, Wang JL1,2,3,4, Cui ZQ2, Zhang Y2,5, Xu F1,2,3,4, Chen YG1,2,3,4.

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Department of Emergency and Chest Pain Center, Qilu Hospital, Shandong University, Ji'nan, China.
Key Laboratory of Cardiovascular Remodeling and Function Research, Ministry of Education and Ministry of Public Health of People's Republic of China, Qilu Hospital, Shandong University, Ji'nan, China.
Institute of Emergency and Critical Care Medicine, Qilu Hospital, Shandong University, Ji'nan, China.
The Key Laboratory of Emergency and Critical Care Medicine Affiliated to Health Commission of Shandong Province, Qilu Hospital, Shandong University, Ji'nan, China.
Department of Cardiology, Qilu Hospital, Shandong University, Ji'nan, China.
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.


Previous studies demonstrated that aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which eliminates ALDH2 activity down to 1%-6%, is a susceptibility gene for coronary disease. Here we investigated the underlying mechanisms based on our prior clinical and experimental studies. Male apoE-/- mice were transfected with GFP, ALDH2-overexpression and ALDH2-RNAi lentivirus respectively (n=20 each) after constrictive collars were placed around the right common carotid arteries. Consequently, ALDH2 gene silencing led to an increased en face plaque area, more unstable plaque with heavier accumulation of lipids, more macrophages, less smooth muscle cells and collagen, which were associated with aggravated inflammation. However, ALDH2 overexpression displayed opposing effects. We also found that ALDH2 activity decreased in atherosclerotic plaques of human and aged apoE-/- mice. Moreover, in vitro experiments with human umbilical vein endothelial cells further illustrated that, inhibition of ALDH2 activity resulted in elevating inflammatory molecules, an increase of nuclear translocation of NF-κB, and enhanced phosphorylation of NF-κB p65, AP-1 c-Jun, Jun-N terminal kinase and p38 MAPK, while ALDH2 activation could trigger contrary effects. These findings suggested that ALDH2 can influence plaque development and vulnerability, and inflammation via MAPK, NF-κB and AP-1 signaling pathways.


ALDH2; MAPK signaling pathway; Pathology Section; atherosclerotic plaque vulnerability; inflammation; polymorphism

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