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The proatherosclerotic function of indoleamine 2, 3- dioxygenase 1 in the developmental stage of atherosclerosis

查看全文 作　　者：Heng [1]Liang;Mantian [2]Chen;Fangfei [1]Qi;Lei [1]Shi;Zhenzhen [1]Duan;Ruoyu [1]Yang;Jinchao [1]He;Bin [3]Lou;Yigang [2]Li;Qing [1]Yang 高影响力作者 机构地区：[1]State Key Laboratory of Genetic Engineering,Department of Biochemistry,School of Life Sciences,Fudan University,Shanghai,China;[2]Department of Cardiovascular Diseases,Xinhua Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai,China;[3]School of Pharmacy,Fudan University,Shanghai,China高影响力机构 出　　处：《Signal Transduction and Targeted Therapy》索引2019年第4卷第1期,共14页高影响力期刊 基　　金：This work was supported by the National Key R&D Program of China(NO.2016YFC1303503);the Key Biomedical Program of Shanghai(NO.17431902200 and 18431902600);the Open Research Fund of State Key Laboratory of Genetic Engineering of Fudan University(NO.SKLGE1816). 摘　　要：The discrepancy of indoleamine 2,3-dioxygenase 1(IDO1)function in atherosclerosis has been noted.Compared to the protective effect of IDO1 against established atherogenesis,the role of IDO1 in the developmental process of atherosclerosis is still unclear.Here,the expression patterns and activities of IDO1 and its isoenzyme tryptophan 2,3-dioxygenase(TDO)in aortas and blood samples of patients with atherosclerosis were investigated.IDO1 and TDO were colocalized with CD3-positive lymphocytes and CD68-positive macrophages in atherosclerotic lesions.The expression and activity of IDO1 and TDO increased with the grade of the histological classification in early atherosclerosis(grade I,II),but the increase did not continue in advanced atherosclerosis(grade III).Treatment of THP-1 macrophages(THP-M)with oxidized low-density lipoprotein(oxLDL)induced the expression of IDO1 via the PI3K/Akt/NF-κB pathway,indicating the potential function of IDO1 in foam cells.Before and after treatment with oxLDL on THP-M,IFN-γ-induced IDO1 exhibited different degrees of promotion on foaming,inflammatory factor production and cell apoptosis.Finally,we found that the IDO1 inhibitor 1-methyl-tryptophan could elevate the high-density lipoprotein cholesterol level in serum and reduce the area of the aortic atherosclerotic lesions in high-fat diet-fed ApoE−/−mice.Our study indicated that IDO1 played a complicated and unfixed role in the entire process of atherogenesis,despite the atheroprotective role in established atherosclerosis.IDO1 also had proatherosclerotic functions in the developmental stages of atherosclerosis.Modulation of IDO1 could be a good method for alleviating atherosclerosis. 关 键 词：PI3K/AKT ATHEROSCLEROSIS protective
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