SynthesisJournal of innate immunity2016
Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis.
Synthesis in Journal of innate immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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 78 papers, 2 of them syntheses 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.
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
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 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
- Relationship Between Hypovitaminosis C, Obesity, and Features of Metabolic Syndrome-A Narrative Review.Nutrition reviews · 2026Review
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Transforming growth factor beta reduces proprotein convertase subtilisin/kexin type 9 in the supernatant of hepatic stellate cells.World journal of hepatology · 2026Article
- Relationship between lipoprotein(a) and PCSK9 in angiogram-proven premature coronary artery disease in an Asian cohort.Scientific reports · 2026Article
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- PCSK9 Promotes Platelet Activation and NET Formation, Aggravating Pulmonary Microthrombosis in Sepsis-Induced Lung Injury.Biomedicines · 2025Article
- Profiles of PCSK9, SREBP-2, and histopathology in COVID-19 and non-COVID-19 critical illness.BMC infectious diseases · 2025Article
- PCSK9 Inhibitors: A Potential Priority Choice for Lipid Management in Patients with Diabetic Kidney Disease.Drugs · 2025Review
- Approaches for Identifying LncRNA-Associated Proteins for Therapeutic Targets and Cancer Biomarker Discovery.Targets (Basel) · 2025Article
- PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.Molecular and cellular biochemistry · 2025Article
- The Role of Olive Oil in Cardiometabolic Risk.Metabolites · 2025Review
- Elevated plasma soluble lectin-like oxidised low-density lipoprotein receptor 1 as an independent prognostic biomarker in sepsis.Lipids in health and disease · 2025Article
- Protective impact of circulating ω-3 PUFAs on sepsis susceptibility throughFrontiers in medicine · 2025Article
- PCSK9 in T-cell function and the immune response.Biomarker research · 2024Review
- Cholesterol and Cholesterol-Lowering Medications in COVID-19-An Unresolved Matter.International journal of molecular sciences · 2024Review
- Proprotein Convertase Subtilisin/Kexin Type 9 Induction in COVID-19 Is Poorly Associated with Disease Severity and Cholesterol Levels.Infectious disease reports · 2024Article
- Assessment of serum proprotein convertase subtilisin/kexin type 9 in pediatric sepsis syndrome.Scientific reports · 2024Article
- TRENDS IN CHOLESTEROL AND LIPOPROTEINS ARE ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME INCIDENCE AND DEATH AMONG SEPSIS PATIENTS.Shock (Augusta, Ga.) · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeWe have recently shown that PCSK9 reduces the clearance of endotoxin and is therefore a critical regulator of the innate immune response during infection. However, plasma PCSK9 levels during human sepsis and their relationship to outcomes are not known. Our objective was to determine the relationship between plasma PCSK9 levels and the rate of endotoxin clearance, and then correlate PCSK9 levels with the development of acute organ failures in a cohort of patients with sepsis.
methodsUsing human hepatocyte cells, we determined the threshold at which PCSK9 is able to reduce Escherichia coli endotoxin uptake by cultured human hepatocytes. In a single-centre observational cohort at St. Paul's Hospital in Vancouver, Canada, we recruited 200 patients who activated our Emergency Department's sepsis protocol and measured plasma PCSK9 and lipid levels at triage and throughout the admission. Outcomes were the development of sepsis-induced cardiovascular or respiratory failure.
resultsWe reviewed the literature and determined that the normal human range of PCSK9 found in plasma is 170-220 ng/ml, while levels of 250 ng/ml and above reduced E. coli endotoxin clearance in cultured human hepatocytes. In septic patients, the median levels associated with new-onset respiratory and cardiovascular failure were 370 (250-500) and 380 (270-530) ng/ml, respectively, versus 270 (220-380) ng/ml in patients who did not go on to develop any organ failure (p = 0.003 and 0.005, respectively).
conclusionsPlasma PCSK9 levels are greatly increased in sepsis. At normal levels, PCSK9 has no influence upon hepatocyte bacterial endotoxin clearance, but as levels rise, there is a progressive inhibition of clearance. During sepsis, PCSK9 levels are highly correlated with the development of subsequent multiple organ failure. Inhibition of PCSK9 activity is an attractive target for treating the spectrum of sepsis and septic shock.
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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.