ArticleJournal of lipid research2013
Bile acid and sterol metabolism with combined HMG-CoA reductase and PCSK9 suppression.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Hepatic Cholesterol Regulation Through Multi-Botanical Extract Targeting of the PCSK9-LDLr-SREBP-2 Axis in HepG2 Cells.Biomedicines · 2026Article
- Combinatorial Effects of Terpene, Chenodeoxycholic Acid, and Ursodeoxycholic Acid on Common Bile Duct Stone Recurrence and Gallbladder Stone Dissolution.Journal of clinical medicine · 2024Article
- MicroRNA-206 as a potential cholesterol-lowering drug is superior to statins in mice.Journal of lipid research · 2024Article
- Cholesterol and COVID-19-therapeutic opportunities at the host/virus interface during cell entry.Life science alliance · 2024Review
- An Analysis of the Gut Microbiota and Related Metabolites following PCSK9 Inhibition in Statin-Treated Patients with Elevated Levels of Lipoprotein(a).Microorganisms · 2024Article
- Anti-PCSK9 Treatment Attenuates Liver Fibrosis via Inhibiting Hypoxia-Induced Autophagy in Hepatocytes.Inflammation · 2023Article
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- Atorvastatin Modulates Bile Acid Homeostasis in Mice with Diet-Induced Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2021Article
- Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend.Frontiers in pharmacology · 2021Article
- Atorvastatin Decreases Renal Menaquinone-4 Formation in C57BL/6 Male Mice.The Journal of nutrition · 2019Article
- Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018Review
- FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.Journal of lipid research · 2018Article
- Statins redux: A re-assessment of how statins lower plasma cholesterol.World journal of diabetes · 2017Review
- E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in the liver.JCI insight · 2017Article
- Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation.The Journal of experimental medicine · 2017Article
- Article
- Investigation of Liver Injury ofFrontiers in pharmacology · 2017Article
- Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice.Journal of lipid research · 2016Article
- PCSK9 deficiency unmasks a sex- and tissue-specific subcellular distribution of the LDL and VLDL receptors in mice.Journal of lipid research · 2015Article
- Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol.Journal of lipid research · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proprotein convertase subtilisin-kexin-9 (PCSK9) inhibition markedly augments the LDL lowering action of statins. The combination is being evaluated for long-term effects on atherosclerotic disease outcomes. However, effects of combined treatment on hepatic cholesterol and bile acid metabolism have not yet been reported. To study this, PCSK9-Y119X mutant (knockout) and wild-type mice were treated with or without atorvastatin for 12 weeks. Atorvastatin progressively lowered plasma LDL in each group, but no differences in liver cholesterol, cholesterol ester, or total bile acid concentrations, or in plasma total bile acid levels were seen. In contrast, atorvastatin increased fecal total bile acids (≈ 2-fold, P < 0.01) and cholesterol concentrations (≈ 3-fold, P < 0.01) versus controls for both PCSK9-Y119X and wild-type mice. All 14 individual bile acids resolved by LC-MS, including primary, secondary, and conjugated species, reflected similar increases. Expression of key liver bile acid synthesis genes CYP7A1 and CYP8B1 were ≈ 2.5-fold higher with atorvastatin in both strains, but mRNA for liver bile acid export and reuptake transporters and conjugating enzymes were not unaffected. The data suggest that hepatocyte cholesterol and bile acid homeostasis is maintained with combined PCSK9 and HMG-CoA reductase inhibition through efficient liver enzymatic conversion of LDL-derived cholesterol into bile acids and excretion of both, with undisturbed enterohepatic recycling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.