title: Aldehyde dehydrogenase 2 inhibits inflammatory response and regulates atherosclerotic plaque.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chang
authors.initials: C
authors.lastname: Pan
authors.affiliation: 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.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Xing
authors.affiliation: 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.|Department of Cardiology, Qilu Hospital, Shandong University, Ji'nan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying-Mei
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lue-Tao
authors.initials: LT
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Shu-Jian
authors.initials: SJ
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xu-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Qiu-Huan
authors.initials: QH
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhao-Qiang
authors.initials: ZQ
authors.lastname: Cui
authors.affiliation: 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.|Department of Cardiology, Qilu Hospital, Shandong University, Ji'nan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Chen
mesh_terms: D000367:Age Factors; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003327:Coronary Disease / Q000097:blood / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D000074085:Mice, Knockout, ApoE; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008055:Lipids; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; C096127:ALDH2 protein, human; C515029:ALDH2 protein, mouse; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ALDH2; MAPK signaling pathway; Pathology Section; atherosclerotic plaque vulnerability; inflammation; polymorphism