ArticleScientific reports2018
Low-density lipoprotein (LDL)-dependent uptake of Gram-positive lipoteichoic acid and Gram-negative lipopolysaccharide occurs through LDL receptor.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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.
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.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects.Biomolecules · 2020Trial
- NicheProt: Cell-type-resolved proteomics of tissue compartments.Science advances · 2026Article
- The dual role of lipoteichoic acid: from immune modulation to therapeutic applications in disease treatment.Inflammopharmacology · 2026Review
- Flavonoids in Plants and Human Health: From Biosynthesis to Neurodevelopmental and Neurodegenerative Disorders.Molecules (Basel, Switzerland) · 2025Review
- Article
- Probiotics and Prebiotics in Post-Myocardial Infarction Rehabilitation: Mechanisms, Benefits, and Future Directions.Current nutrition reports · 2025Review
- Effects of Combined Periodontal, Endodontic, and Dentoalveolar Surgical Treatments on Laboratory Parameters in Patients with Hyperlipidemia-A Clinical Interventional Study.Journal of clinical medicine · 2025Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival From Sepsis.Critical care explorations · 2023Article
- The Anti-Thrombotic Effects of PCSK9 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Hacking the Immune Response to Solid Tumors: Harnessing the Anti-Cancer Capacities of Oncolytic Bacteria.Pharmaceutics · 2023Review
- Plasma Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) as a Possible Biomarker for Severe COVID-19.Viruses · 2023Article
- Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1.Critical care (London, England) · 2023Observational
- A Review of Classification, Biosynthesis, Biological Activities and Potential Applications of Flavonoids.Molecules (Basel, Switzerland) · 2023Review
- The evolving landscape of PCSK9 inhibition in cancer.European journal of pharmacology · 2023Review
- Lipoproteins act as vehicles for lipid antigen delivery and activation of invariant natural killer T cells.JCI insight · 2023Article
- Targeting UGCG Overcomes Resistance to Lysosomal Autophagy Inhibition.Cancer discovery · 2023Article
- Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1.Research square · 2023Article
- Impact of High-Density Lipoproteins on Sepsis.International journal of molecular sciences · 2022Review
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are bacterial lipids that stimulate pro-inflammatory cytokine production, thereby exacerbating sepsis pathophysiology. Proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulates uptake of cholesterol by downregulating hepatic lipoprotein receptors, including low-density lipoprotein (LDL) receptor (LDLR) and possibly LDLR-related protein-1 (LRP1). PCSK9 also negatively regulates Gram-negative LPS uptake by hepatocytes, however this mechanism is not completely characterized and mechanisms of Gram-positive LTA uptake are unknown. Therefore, our objective was to elucidate the mechanisms through which PCSK9 regulates uptake of LTA and LPS by investigating the roles of lipoproteins and lipoprotein receptors. Here we show that plasma PCSK9 concentrations increase transiently over time in septic and non-septic critically ill patients, with highly similar profiles over 14 days. Using flow cytometry, we demonstrate that PCSK9 negatively regulates LDLR-mediated uptake of LTA and LPS by HepG2 hepatocytes through an LDL-dependent mechanism, whereas LRP1 and high-density lipoprotein do not contribute to this uptake pathway. Bacterial lipid uptake by hepatocytes was not associated with cytokine production or hepatocellular injury. In conclusion, our study characterizes an LDL-dependent and LDLR-mediated bacterial lipid uptake pathway regulated by PCSK9, and provides evidence in support of PCSK9 inhibition as a potential therapeutic strategy for sepsis.
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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.