Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages
2019-02
Source PublicationREDOX BIOLOGY
ISSN2213-2317
Volume21
Status已发表
DOI10.1016/j.redox.2018.101069
AbstractDysregulation 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.
KeywordCholesterol/metabolism LDL oxidation Lipidomics CVD Cholesterol ester hydroperoxides Cholesterol uptake Lipid peroxidation LXR LDLR
Indexed BySCI ; SCIE
Language英语
Funding ProjectChinese Academy of Sciences[ZDBS-SSW-DQC-02]
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000462926900011
PublisherELSEVIER SCIENCE BV
WOS KeywordLOW-DENSITY-LIPOPROTEIN ; PHOSPHOLIPID OXIDATION-PRODUCTS ; MINIMALLY MODIFIED LDL ; LIPID-PEROXIDATION ; LINOLEATE HYDROPEROXIDES ; MASS SPECTROMETRY ; NUCLEAR RECEPTORS ; IN-VITRO ; LXR ; METABOLISM
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34254
Collection生命科学与技术学院_博士生
生命科学与技术学院_特聘教授组_尹慧勇组
生命科学与技术学院_硕士生
Corresponding AuthorYin, Huiyong
Affiliation
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
First Author AffilicationSchool of Life Science and Technology
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
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.
APA Guo, Shuyuan.,Lu, Jianhong.,Zhuo, Yujuan.,Xiao, Mengqing.,Xue, Xinli.,...&Yin, Huiyong.(2019).Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages.REDOX BIOLOGY,21.
MLA Guo, Shuyuan,et al."Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages".REDOX BIOLOGY 21(2019).
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