ArticleArteriosclerosis, thrombosis, and vascular biology2013
Ezetimibe inhibits hepatic Niemann-Pick C1-Like 1 to facilitate macrophage reverse cholesterol transport in mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.Arteriosclerosis, thrombosis, and vascular biology · 2017Trial
- A Comprehensive, Updated Review of Ezetimibe: Evidence-Based Clinical Use for Atherosclerotic Cardiovascular Disease.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2026Review
- Niemann-Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors.Current issues in molecular biology · 2026Review
- Ezetimibe Normalizes Dietary Cholesterol-Induced Exacerbation of Liver Injury in Alcohol-Fed Mice.Biomolecules · 2026Article
- Potential lipid-lowering effects of preussin B on inhibition of intestinal cholesterol absorption: integrative mechanisms of action and proteomic analysis.Frontiers in pharmacology · 2025Article
- Laminarin Reduces Cholesterol Uptake and NPC1L1 Protein Expression in High-Fat Diet (HFD)-Fed Mice.Marine drugs · 2023Article
- Appropriateness of Dyslipidemia Management Strategies in Post-Acute Coronary Syndrome: A 2023 Update.Metabolites · 2023Review
- The Hypocholesterolemic Potential of the Edible AlgaeFoods (Basel, Switzerland) · 2023Article
- m6A-related bioinformatics analysis and functional characterization reveals that METTL3-mediated NPC1L1 mRNA hypermethylation facilitates progression of atherosclerosis via inactivation of the MAPK pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Transintestinal cholesterol excretion in health and disease.Current atherosclerosis reports · 2022Review
- Ezetimibe promotes CYP7A1 and modulates PPARs as a compensatory mechanism in LDL receptor-deficient hamsters.Lipids in health and disease · 2020Article
- Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux.Journal of lipid research · 2016Article
- A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion.Trends in pharmacological sciences · 2015Review
- Cholesterol and lipoprotein metabolism: Early Career Committee contribution.Arteriosclerosis, thrombosis, and vascular biology · 2014Review
- Differential impact of hepatic deficiency and total body inhibition of MTP on cholesterol metabolism and RCT in mice.Journal of lipid research · 2014Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveControversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective of this study was to examine the role of biliary cholesterol secretion in modulating macrophage RCT in Niemann-Pick C1-Like 1 (NPC1L1) liver only (L1(LivOnly)) mice, an animal model that is defective in both biliary sterol secretion and intestinal sterol absorption, and determine whether NPC1L1 inhibitor ezetimibe facilitates macrophage RCT by inhibiting hepatic NPC1L1. APPROACH AND
resultsL1(LivOnly) mice were generated by crossing NPC1L1 knockout (L1-KO) mice with transgenic mice overexpressing human NPC1L1 specifically in liver. Macrophage-to-feces RCT was assayed in L1-KO and L1(LivOnly) mice injected intraperitoneally with [(3)H]-cholesterol-labeled peritoneal macrophages isolated from C57BL/6 mice. Inhibition of biliary sterol secretion by hepatic overexpression of NPC1L1 substantially reduced transport of [(3)H]-cholesterol from primary peritoneal macrophages to the neutral sterol fraction in bile and feces in L1(LivOnly) mice without affecting tracer excretion in the bile acid fraction. Ezetimibe treatment for 2 weeks completely restored both biliary and fecal excretion of [(3)H]-tracer in the neutral sterol fraction in L1(LivOnly) mice. High-density lipoprotein kinetic studies showed that L1(LivOnly) mice compared with L1-KO mice had a significantly reduced fractional catabolic rate without altered hepatic and intestinal uptake of high-density lipoprotein-cholesterol ether.
conclusionsIn mice lacking intestinal cholesterol absorption, macrophage-to-feces RCT depends on efficient biliary sterol secretion, and ezetimibe promotes macrophage RCT by inhibiting hepatic NPC1L1 function.
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Registered trials
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