ArticleJournal of cellular and molecular medicine2017
Simvastatin promotes NPC1-mediated free cholesterol efflux from lysosomes through CYP7A1/LXRα signalling pathway in oxLDL-loaded macrophages.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- The Niemann-Pick C1 Protein of Patients with Hepatocellular Carcinoma Is Associated with Survival Time in Males and Tumor Size in Females.Biomedicines · 2025Article
- Twinkling Peptide Nanoemulsions Enable Precision Ultrasound Detection of Atherosclerotic Plaques.Advanced functional materials · 2025Article
- ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-FedArteriosclerosis, thrombosis, and vascular biology · 2024Article
- Schisandrin A inJournal of microbiology and biotechnology · 2024Article
- Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.Frontiers in pharmacology · 2024Review
- Effects ofMetabolites · 2022Article
- Hepatocyte-Derived Prostaglandin E2-Modulated Macrophage M1-Type Polarization via mTOR-NPC1 Axis-Regulated Cholesterol Transport from Lysosomes to the Endoplasmic Reticulum in Hepatitis B Virus x Protein-Related Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2022Article
- Niacin promotes the efflux of lysosomal cholesterol from macrophages via the CD38/NAADP signaling pathway.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Cardioprotective cytokine interleukin-33 is up-regulated by statins in human cardiac tissue.Journal of cellular and molecular medicine · 2018Article
- Gut Microbiota Modulation Attenuated the Hypolipidemic Effect of Simvastatin in High-Fat/Cholesterol-Diet Fed Mice.Journal of proteome research · 2017Article
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Statins, 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, are the first-line medications prescribed for the prevention and treatment of coronary artery diseases. The efficacy of statins has been attributed not only to their systemic cholesterol-lowering actions but also to their pleiotropic effects that are unrelated to cholesterol reduction. These pleiotropic effects have been increasingly recognized as essential in statins therapy. This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression. With simultaneous nile red and filipin staining, analysis of confocal/multi-photon imaging demonstrated that simvastatin markedly attenuated unesterified (free) cholesterol buildup in macrophages loaded with oxidized low-density lipoprotein but had little effect in reducing the sizes of cholesteryl ester-containing lipid droplets; the reduction in free cholesterol was mainly attributed to decreases in lysosome-compartmentalized cholesterol. Functionally, the egression of free cholesterol from lysosomes attenuated pro-inflammatory cytokine secretion. It was determined that the reduction of lysosomal free cholesterol buildup by simvastatin was due to the up-regulation of Niemann-Pick C1 (NPC1), a lysosomal residing cholesterol transporter. Moreover, the enhanced enzymatic production of 7-hydroxycholesterol by cytochrome P450 7A1 and the subsequent activation of liver X receptor α underscored the up-regulation of NPC1. These findings reveal a novel pleiotropic effect of simvastatin in affecting lysosomal cholesterol efflux in macrophages and the associated significance in the treatment of atherosclerosis.
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