ArticleScientific reports2019
PCSK9 inhibition as a novel therapeutic target for alcoholic liver disease.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging.Molecular psychiatry · 2022Pooled it
- PCSK9 inhibition attenuates alcohol-induced cardiovascular dysfunction and links hepatic lipid accumulation to impaired myocardial contractile reserve.GeroScience · 2026Article
- Identification and evaluation of a lipid-lowering small compound as a PCSK9 inhibitor.Journal of advanced research · 2026Article
- Systemic PCSK9 elevation characterises autoimmune liver disease across sexes.Scientific reports · 2025Article
- A Pre-Clinical Study on the Use of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor PEP 2-8 to Mitigate Ischemic Injury in a Rat Marginal Donor Model.International journal of molecular sciences · 2025Article
- Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells.Non-coding RNA research · 2025Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- Evaluating the effect of the antiPCSK9 vaccine on systemic inflammation and oxidative stress in an experimental mouse model.Cardiology journal · 2025Article
- Unraveling the rapid progression of non-target lesions: risk factors and the therapeutic potential of PCSK9 inhibitors in post-PCI patients.BMC cardiovascular disorders · 2024Article
- PCSK9 Inhibitors and Anthracyclines: The Future of Cardioprotection in Cardio-Oncology.Hearts (Basel, Switzerland) · 2024Article
- Genetic association of lipid and lipid-lowering drug target genes with atopic dermatitis: a drug target Mendelian randomization study.Scientific reports · 2024Article
- Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Improves the Vascular Function of Arteriovenous Fistula in Rats with Hyperglycemia.Acta Cardiologica Sinica · 2024Article
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- PCSK9: an emerging player in cardiometabolic aging and its potential as a therapeutic target and biomarker.GeroScience · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Data-driven transcriptomics analysis identifies PCSK9 as a novel key regulator in liver aging.GeroScience · 2023Article
- PCSK9, A Promising Novel Target for Age-Related Cardiovascular Dysfunction.JACC. Basic to translational science · 2023Article
- Dietary cholesterol in alcohol-associated liver disease.Immunometabolism (Cobham, Surrey) · 2023Review
- PCSK9 inhibitors suppress oxidative stress and inflammation in atherosclerotic development by promoting macrophage autophagy.American journal of translational research · 2023Article
- PCSK9 regulates the efficacy of immune checkpoint therapy in lung cancer.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Alcoholic liver disease (ALD) causes significant morbidity and mortality, and pharmacological treatment options are limited. In this study, we evaluated the PCSK9 inhibitor alirocumab, a monoclonal antibody that robustly reduces low-density lipoprotein cholesterol (LDL-C), for the treatment of ALD using a rat model of chronic alcohol exposure. Alirocumab (50 mg/kg) or vehicle was administered weekly for 6 weeks to rats receiving a 12% alcohol liquid diet or an isocaloric control diet. At the end of the alcohol exposure protocol, serum and liver samples were obtained for molecular characterization and histopathological analysis. PCSK9 inhibition with alirocumab attenuated alcohol-induced hepatic triglyceride accumulation through regulation of lipid metabolism (mRNA expression of modulators of fatty acid synthesis (FAS) and catabolism (PPARα and CPT1)), hepatocellular injury (ALT), hepatic inflammation (mRNA expression of pro-inflammatory cytokines/chemokines (TNFa, IL-1β, IL-22, IL-33, IL-17α, IL-2, MIP-2, and MCP-1), and neutrophil infiltration (myeloperoxidase staining)). Alirocumab treatment also attenuated alcohol-induced PCSK9 mRNA elevation and upregulated LDL-receptor (LDL-R) via modulation of the transcription factors (SREBP-1, SREBP-2, and E2F1) in liver. We demonstrated that chronic anti-PCSK9 treatment using the monoclonal antibody alirocumab attenuated alcohol-induced steatohepatitis in the rat model. Given the large unmet clinical need for effective and novel treatments for ALD, anti-PCSK9 treatment with the monoclonal antibody that spares liver metabolism is a viable new therapeutic possibility. Future studies are needed to elucidate the exact role of PCSK9 in ALD and alcohol use disorder (AUD) and to evaluate efficacy and safety of anti-PCSK9 treatment in clinical populations with ALD/AUD.
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What Socratic holds
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 Socratic graph.