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

doi:10.1016/j.redox.2018.101069

	Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages
	Guo, Shuyuan1,2,3 ; Lu, Jianhong 1,2; Zhuo, Yujuan1,2,3 ; Xiao, Mengqing1,2,3 ; Xue, Xinli 1,2; Zhong, Shanshan 1,2; Shen, Xia1,2,3 ; Yin, Chunzhao1,2,3 ; Li, Luxiao1,2,3 ; Chen, Qun 1,2; Zhu, Mingjiang 1; Chen, Buxing 4; Zhao, Mingming 5,6; Zheng, Lemin 5,6; Tao, Yongzhen 1; Yin, Huiyong1,2,3,7
	2019-02
发表期刊	REDOX BIOLOGY (IF:10.7[JCR-2023],11.7[5-Year])
ISSN	2213-2317
卷号	21
发表状态	已发表
DOI	10.1016/j.redox.2018.101069
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.
关键词	Cholesterol/metabolism LDL oxidation Lipidomics CVD Cholesterol ester hydroperoxides Cholesterol uptake Lipid peroxidation LXR LDLR
收录类别	SCI ; SCIE
语种	英语
资助项目	Chinese Academy of Sciences[ZDBS-SSW-DQC-02]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000462926900011
出版者	ELSEVIER SCIENCE BV
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
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34254
专题	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
通讯作者	Yin, Huiyong
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
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
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.
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).