ArticlePloS one2016
Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03869073 (Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Efficacy and Safety of Evolocumab for PCSK9 Lowering in Early Acute Sepsis), which is not on this map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Efficacy and Safety of Evolocumab for PCSK9 Lowering in Early Acute Sepsis
Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology.Cardiovascular research · 2019Guideline
- The Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Cardiovascular Homeostasis: A Non-Systematic Literature Review.Current cardiology reviews · 2017Pooled it
- Safety and Tolerability of Xanthohumol in Adults With Crohn's Disease: Results of a Triple-Masked, Randomized, Placebo-Controlled Phase 2 Trial.Molecular nutrition & food research · 2026Trial
- Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects.Biomolecules · 2020Trial
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Bornyl Acetate and Menthol Provide Neuroprotection Against Lipopolysaccharide-Induced Alzheimer's Disease-Like Condition in C57BL/6 Mice by Downregulating NARC-1 Lipid Antagonist.Molecular neurobiology · 2025Article
- High-density lipoproteins alleviate the endotoxin burden in patients with peritonitis and sepsis: The LIPS study.European journal of clinical investigation · 2025Observational
- Profiles of PCSK9, SREBP-2, and histopathology in COVID-19 and non-COVID-19 critical illness.BMC infectious diseases · 2025Article
- High-density lipoprotein: a biomarker and therapeutic target in sepsis.Critical care (London, England) · 2025Review
- Investigating the expression of CD180, LY96, VCAM-1, and CSF2RB in the lipopolysaccharide response pathway across different liver cirrhosis etiologies.Molecular biology reports · 2025Article
- The balance between proinflammatory, "bad", and immunomodulatory, "good", lipopolysaccharide for understanding gut-derived systemic inflammation.Frontiers in immunology · 2025Review
- Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality.Critical care (London, England) · 2024Article
- Review
- Tissue-resident bacteria in metabolic diseases: emerging evidence and challenges.Nature metabolism · 2024Review
- TRENDS IN CHOLESTEROL AND LIPOPROTEINS ARE ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME INCIDENCE AND DEATH AMONG SEPSIS PATIENTS.Shock (Augusta, Ga.) · 2024Article
- Proteomic Evolution from Acute to Post-COVID-19 Conditions.Journal of proteome research · 2024Article
- The liver's dilemma: sensing real danger in a sea of PAMPs: the (arterial) sinusoidal segment theory.Frontiers in immunology · 2024Review
- Anti-PCSK9 Treatment Attenuates Liver Fibrosis via Inhibiting Hypoxia-Induced Autophagy in Hepatocytes.Inflammation · 2023Article
- Host extracellular vesicles confer cytosolic access to systemic LPS licensing non-canonical inflammasome sensing and pyroptosis.Nature cell biology · 2023Article
- Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study.BMC emergency medicine · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Sepsis is the leading cause of death in critically ill patients. While decreased Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) function improves clinical outcomes in murine and human sepsis, the mechanisms involved have not been fully elucidated. We tested the hypothesis that lipopolysaccharide (LPS), the major Gram-negative bacteria endotoxin, is cleared from the circulation by hepatocyte Low Density Lipoprotein Receptors (LDLR)-receptors downregulated by PCSK9. We directly visualized LPS uptake and found that LPS is rapidly taken up by hepatocytes into the cell periphery. Over the course of 4 hours LPS is transported towards the cell center. We next found that clearance of injected LPS from the blood was reduced substantially in Ldlr knockout (Ldlr-/-) mice compared to wild type controls and, simultaneously, hepatic uptake of LPS was also reduced in Ldlr-/- mice. Specifically examining the role of hepatocytes, we further found that primary hepatocytes isolated from Ldlr-/- mice had greatly decreased LPS uptake. In the HepG2 immortalized human hepatocyte cell line, LDLR silencing similarly resulted in decreased LPS uptake. PCSK9 treatment reduces LDLR density on hepatocytes and, therefore, was another independent strategy to test our hypothesis. Incubation with PCSK9 reduced LPS uptake by hepatocytes. Taken together, these findings demonstrate that hepatocytes clear LPS from the circulation via the LDLR and PCSK9 regulates LPS clearance from the circulation during sepsis by downregulation of hepatic LDLR.
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What OpenQuestion 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 OpenQuestion graph.