ArticleThe Journal of biological chemistry2013
FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Article
- Subcellular sirtuin signaling networks: pivotal regulators of cardiovascular homeostasis and remodeling.Journal of molecular histology · 2026Review
- Article
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- PCSK9 inhibition ameliorates microplastic-induced endothelial redox imbalance via SIRT6 modulation.Cellular & molecular biology letters · 2025Article
- Regulatory mechanisms of hepatocyte PCSK9 expression: translating mechanistic insights into potential nutraceuticals.Chinese medicine · 2025Review
- Methionine Metabolism Dictates PCSK9 Expression and Antitumor Potency of PD-1 Blockade in MSS Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Article
- Sirtuin 6 mediates the therapeutic effect of endometrial regenerative cell-derived exosomes in alleviation of acute transplant rejection by weakening c-myc-dependent glutaminolysis.Frontiers in cell and developmental biology · 2025Article
- NAD Pathways in Diabetic Coronary Heart Disease: Unveiling the Key Players.Current medicinal chemistry · 2025Review
- Exploring the Pleiotropy of PCSK9: A Wide Range of Influences from Lipid Regulation to Extrahepatic Function.Journal of inflammation research · 2025Review
- Impaired SUMOylation of FoxA1 promotes nonalcoholic fatty liver disease through down-regulation of Sirt6.Cell death & disease · 2024Article
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- SIRT6 in Regulation of Mitochondrial Damage and Associated Cardiac Dysfunctions: A Possible Therapeutic Target for CVDs.Cardiovascular toxicology · 2024Review
- Gallic Acid Can Promote Low-Density Lipoprotein Uptake in HepG2 Cells via Increasing Low-Density Lipoprotein Receptor Accumulation.Molecules (Basel, Switzerland) · 2024Article
- Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Elevated LDL-cholesterol is a risk factor for the development of cardiovascular disease. Thus, proper control of LDL-cholesterol homeostasis is critical for organismal health. Genetic analysis has identified PCSK9 (proprotein convertase subtilisin/kexin type 9) as a crucial gene in the regulation of LDL-cholesterol via control of LDL receptor degradation. Although biochemical characteristics and clinical implications of PCSK9 have been extensively investigated, epigenetic regulation of this gene is largely unknown. In this work we have discovered that Sirt6, an NAD(+)-dependent histone deacetylase, plays a critical role in the regulation of the Pcsk9 gene expression in mice. Hepatic Sirt6 deficiency leads to elevated Pcsk9 gene expression and LDL-cholesterol as well. Mechanistically, we have demonstrated that Sirt6 can be recruited by forkhead transcription factor FoxO3 to the proximal promoter region of the Pcsk9 gene and deacetylates histone H3 at lysines 9 and 56, thereby suppressing the gene expression. Also remarkably, overexpression of Sirt6 in high fat diet-fed mice lowers LDL-cholesterol. Overall, our data suggest that FoxO3 and Sirt6, two longevity genes, can reduce LDL-cholesterol levels through regulation of the Pcsk9 gene.
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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.