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| Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages | |
| 2019-02 | |
| Source Publication | REDOX BIOLOGY
 |
| ISSN | 2213-2317 |
| Volume | 21 |
| Status | 已发表 |
| DOI | 10.1016/j.redox.2018.101069 |
| Abstract | 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. |
| Keyword | Cholesterol/metabolism LDL oxidation Lipidomics CVD Cholesterol ester hydroperoxides Cholesterol uptake Lipid peroxidation LXR LDLR |
| Indexed By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | Chinese Academy of Sciences[ZDBS-SSW-DQC-02] |
| WOS Research Area | Biochemistry & Molecular Biology |
| WOS Subject | Biochemistry & Molecular Biology |
| WOS ID | WOS:000462926900011 |
| Publisher | ELSEVIER SCIENCE BV |
| WOS Keyword | LOW-DENSITY-LIPOPROTEIN ; PHOSPHOLIPID OXIDATION-PRODUCTS ; MINIMALLY MODIFIED LDL ; LIPID-PEROXIDATION ; LINOLEATE HYDROPEROXIDES ; MASS SPECTROMETRY ; NUCLEAR RECEPTORS ; IN-VITRO ; LXR ; METABOLISM |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://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 Author | Yin, 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 Affilication | School of Life Science and Technology |
| Corresponding Author Affilication | School 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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