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Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages

文献类型：期刊论文

作者Guo, Shuyuan1,2,3; Lu, Jianhong1,2; Zhuo, Yujuan1,2,3; Xiao, Mengqing1,2,3; Xue, Xinli1,2; Zhong, Shanshan1,2; Shen, Xia1,2,3; Yin, Chunzhao1,2,3; Li, Luxiao1,2,3; Chen, Qun1,2
刊名REDOX BIOLOGY
出版日期2019
卷号21期号:-页码:UNSP 101069
ISSN号2213-2317
关键词Cholesterol/metabolism LDL oxidation Lipidomics CVD Cholesterol ester hydroperoxides Cholesterol uptake Lipid peroxidation LXR LDLR
DOI10.1016/j.redox.2018.101069
文献子类Article
英文摘要Dysregulation of cholesterol metabolism represents one of the major risk factors for atherosclerotic cardiovascular disease (CVD). Oxidized cholesterol esters (oxCE) in low-density lipoprotein (LDL) have been implicated in CVD but the underlying mechanisms remain poorly defined. We use a targeted lipidomic approach to demonstrate that levels of oxCEs in human plasma are associated with different types of CVD and significantly elevated in patients with myocardial infarction. We synthesized a major endogenous cholesterol ester hydroperoxide (CEOOH), cholesteryl-13(cis, trans)-hydroperoxy-octadecadienoate (ch-13(c,t)-HpODE) and show that this endogenous compound significantly increases plasma cholesterol level in mice while decrease cholesterol levels in mouse liver and peritoneal macrophages, which is primarily due to the inhibition of cholesterol uptake in macrophages and liver. Further studies indicate that inhibition of cholesterol uptake by ch-13(c,t)-HpODE in macrophages is dependent on LXR alpha-IDOL-LDLR pathway, whereas inhibition on cholesterol levels in hepatocytes is dependent on LXR alpha and LDLR. Consistently, these effects on cholesterol levels by ch-13(c,t)-HpODE are diminished in LDLR or LXR alpha knockout mice. Together, our study provides evidence that elevated plasma cholesterol levels by CEOOHs are primarily due to the inhibition of cholesterol uptake in the liver and macrophages, which may play an important role in the pathogenesis of CVD.
学科主题Biochemistry & Molecular Biology
WOS关键词LOW-DENSITY-LIPOPROTEIN ; PHOSPHOLIPID OXIDATION-PRODUCTS ; MINIMALLY MODIFIED LDL ; LIPID-PEROXIDATION ; LINOLEATE HYDROPEROXIDES ; MASS SPECTROMETRY ; NUCLEAR RECEPTORS ; IN-VITRO ; LXR ; METABOLISM
语种英语
出版者ELSEVIER SCIENCE BV
WOS记录号WOS:000462926900011
版本出版稿
源URL[http://202.127.25.144/handle/331004/1007]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth, SIBS, Shanghai 200031, Peoples R China;
2.Univ Chinese Acad Sci, CAS, Beijing 100049, Peoples R China;
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China;
4.Capital Med Univ, Beijing Tiantan Hosp, Dept Cardiol, Beijing, Peoples R China;
5.Peking Univ, Inst Cardiovasc Sci, Minist Educ, Hlth Sci Ctr, Beijing, Peoples R China;
6.Peking Univ, Inst Syst Biomed, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci,Minist Educ,Hlth Sci C, Beijing, Peoples R China;
7.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing 100000, Peoples R China,
推荐引用方式
GB/T 7714		 Guo, Shuyuan,Lu, Jianhong,Zhuo, Yujuan,et al. Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages[J]. REDOX BIOLOGY,2019,21(-):UNSP 101069.
APA Guo, Shuyuan.,Lu, Jianhong.,Zhuo, Yujuan.,Xiao, Mengqing.,Xue, Xinli.,...&,.(2019).Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages.REDOX BIOLOGY,21(-),UNSP 101069.
MLA Guo, Shuyuan,et al."Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages".REDOX BIOLOGY 21.-(2019):UNSP 101069.

入库方式： OAI收割

来源：上海营养与健康研究所

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