Aldehyde dehydrogenase 2 inhibits inflammatory response and regulates atherosclerotic plaque.
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.
['Pan|Chang|C|', 'Xing|Jun-Hui|JH|', 'Zhang|Cheng|C|', 'Zhang|Ying-Mei|YM|', 'Zhang|Lue-Tao|LT|', 'Wei|Shu-Jian|SJ|', 'Zhang|Ming-Xiang|MX|', 'Wang|Xu-Ping|XP|', 'Yuan|Qiu-Huan|QH|', 'Xue|Li|L|', 'Wang|Jia-Li|JL|', 'Cui|Zhao-Qiang|ZQ|', 'Zhang|Yun|Y|', 'Xu|Feng|F|', 'Chen|Yu-Guo|YG|']
D000367:Age Factors D000071396:Aldehyde Dehydrogenase, Mitochondrial D000818:Animals D002478:Cells, Cultured D003327:Coronary Disease D003331:Coronary Vessels D004195:Disease Models, Animal D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D007249:Inflammation D016086:Lentivirus D008055:Lipids D008264:Macrophages D008297:Male D051379:Mice D000074085:Mice, Knockout, ApoE D058226:Plaque, Atherosclerotic D034622:RNA Interference D034741:RNA, Small Interfering D015398:Signal Transduction D018808:Transcription Factor AP-1 D051996:Transcription Factor RelA D014162:Transfection D048051:p38 Mitogen-Activated Protein Kinases
ALDH2 polymorphism inflammation MAPK signaling pathway Pathology Section atherosclerotic plaque vulnerability