ArticleRedox biology2019
Endogenous cholesterol ester hydroperoxides modulate cholesterol levels and inhibit cholesterol uptake in hepatocytes and macrophages.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 48 citations in OpenAlex.
- The Role of Glutathione Peroxidase 4 in Atherosclerosis: Role and Therapeutic Potential.Reviews in cardiovascular medicine · 2026Review
- Advanced multifunctional nano-delivery platform focusing on treating diseases related to lipid metabolism via targeted intervention in various lipid metabolic processes.Military Medical Research · 2025Review
- Mechanisms of regulation of glycolipid metabolism by natural compounds in plants: effects on short-chain fatty acids.Nutrition & metabolism · 2024Review
- The Role of Nrf2 and Inflammation on the Dissimilar Cardiotoxicity of Doxorubicin in Two-Time Points: a Cardio-Oncology In Vivo Study Through Time.Inflammation · 2024Article
- Examining the expression levels of ferroptosis-related genes in angiographically determined coronary artery disease patients.Molecular biology reports · 2022Article
- Aldehyde dehydrogenase 2 and PARP1 interaction modulates hepatic HDL biogenesis by LXRα-mediated ABCA1 expression.JCI insight · 2022Article
- The clinical translation of eicosanoids and other oxylipins, although challenging, should be actively pursued.Journal of mass spectrometry and advances in the clinical lab · 2021Article
- Analysis of Saliva Lipids in Breast and Prostate Cancer by IR Spectroscopy.Diagnostics (Basel, Switzerland) · 2021Article
- Taurine-Mediated IDOL Contributes to Resolution of Streptococcus uberis Infection.Infection and immunity · 2021Article
- Oxidized LDL Disrupts Metabolism and Inhibits Macrophage Survival by Activating a miR-9/Drp1/Mitochondrial Fission Signaling Pathway.Oxidative medicine and cellular longevity · 2020Article
- Total Glucosides of Peony Protect Cardiomyocytes against Oxidative Stress and Inflammation by Reversing Mitochondrial Dynamics and Bioenergetics.Oxidative medicine and cellular longevity · 2020Article
- From Inert Storage to Biological Activity-In Search of Identity for Oxidized Cholesteryl Esters.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 LXRα-IDOL-LDLR pathway, whereas inhibition on cholesterol levels in hepatocytes is dependent on LXRα and LDLR. Consistently, these effects on cholesterol levels by ch-13(c,t)-HpODE are diminished in LDLR or LXRα 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.
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