Trial reportScience translational medicine2014
PCSK9 is a critical regulator of the innate immune response and septic shock outcome.
Trial report in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 192 papers, 3 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.
PCSK9 Inhibitor: a New Tool to Fight Septic Shock
Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Efficacy and Safety of Evolocumab for PCSK9 Lowering in Early Acute Sepsis
Who cites it
192 citing papers in PubMed, 3 syntheses or guidelines pooled it, 367 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
- Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis.Journal of innate immunity · 2016Pooled it
- Effect of PCSK9 inhibitors on the quality of life in patients with acute coronary syndromes - exploratory analysis of the EMSIACS trial.Scientific reports · 2025Trial
- PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.Journal of the American College of Cardiology · 2023Trial
- Micellar Curcumin: Pharmacokinetics and Effects on Inflammation Markers and PCSK-9 Concentrations in Healthy Subjects in a Double-Blind, Randomized, Active-Controlled, Crossover Trial.Molecular nutrition & food research · 2022Trial
- Polymorphisms of rs2483205 and rs562556 in the PCSK9 gene are associated with coronary artery disease and cardiovascular risk factors.Scientific reports · 2021Trial
- Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects.Biomolecules · 2020Trial
- Colistin dampens fibrinolysis and endothelial activation during endotoxaemia. A randomised, double blind trial.Thrombosis and haemostasis · 2017Trial
- Role of PCSK9 in hallmarks of cancer: From mechanisms to interventions (Review).Oncology letters · 2026Review
- Reduced Serum Endostatin in Premenopausal Women with Lipedema Suggests Altered Vascular Homeostasis.Diseases (Basel, Switzerland) · 2026Article
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Death-associated protein kinase 2 (DAPK2) propagates endoplasmic reticulum stress in macrophages to worsen sepsis through HSPA5-IRE1α axis.Molecular biomedicine · 2026Article
- Combined HDL-BMI Phenotyping Provides Incremental Prognostic Value in Idiopathic Pulmonary Fibrosis.Journal of clinical medicine · 2026Article
- Alirocumab Attenuated Plaque Inflammation and PCSK9-Induced Proinflammatory Signalling in M1 Macrophages Independently of Lipid Lowering.Biomolecules · 2026Article
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- The discovery of PCSK9 as a pivotal point in the prevention of cardiovascular disease.American journal of preventive cardiology · 2025Review
- PCSK9 Promotes Platelet Activation and NET Formation, Aggravating Pulmonary Microthrombosis in Sepsis-Induced Lung Injury.Biomedicines · 2025Article
- PCSK9 Inhibitors: A Potential Priority Choice for Lipid Management in Patients with Diabetic Kidney Disease.Drugs · 2025Review
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
A decrease in the activity of proprotein convertase subtilisin/kexin type 9 (PCSK9) increases the amount of low-density lipoprotein (LDL) receptors on liver cells and, therefore, LDL clearance. The clearance of lipids from pathogens is related to endogenous lipid clearance; thus, PCSK9 may also regulate removal of pathogen lipids such as lipopolysaccharide (LPS). Compared to controls, Pcsk9 knockout mice displayed decreases in inflammatory cytokine production and in other physiological responses to LPS. In human liver cells, PCSK9 inhibited LPS uptake, a necessary step in systemic clearance and detoxification. Pharmacological inhibition of PCSK9 improved survival and inflammation in murine polymicrobial peritonitis. Human PCSK9 loss-of-function genetic variants were associated with improved survival in septic shock patients and a decrease in inflammatory cytokine response both in septic shock patients and in healthy volunteers after LPS administration. The PCSK9 effect was abrogated in LDL receptor (LDLR) knockout mice and in humans who are homozygous for an LDLR variant that is resistant to PCSK9. Together, our results show that reduced PCSK9 function is associated with increased pathogen lipid clearance via the LDLR, a decreased inflammatory response, and improved septic shock outcome.
Indexed as
Identifiers
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.