ArticleScientific reports2019
Reduced Proprotein convertase subtilisin/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in Gram positive septic shock patients.
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 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects.Biomolecules · 2020Trial
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Proteomic Evolution from Acute to Post-COVID-19 Conditions.Journal of proteome research · 2024Article
- Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival From Sepsis.Critical care explorations · 2023Article
- Elevated circulating PCSK9 level is associated with 28-day mortality in patients with sepsis: a prospective cohort study.BMC emergency medicine · 2023Article
- 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
- The evolving landscape of PCSK9 inhibition in cancer.European journal of pharmacology · 2023Review
- Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Review
- Impact of High-Density Lipoproteins on Sepsis.International journal of molecular sciences · 2022Review
- Article
- Review
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- Article
- Low PCSK-9 levels Are Associated with Favorable Neurologic Function after Resuscitation from out of Hospital Cardiac Arrest.Journal of clinical medicine · 2020Article
- PCSK9: A Potential Therapeutic Target for Sepsis.Journal of immunology research · 2020Review
- Association of Serum PCSK9 Levels with Antibiotic Resistance and Severity of Disease in Patients with Bacterial Infections Admitted to Intensive Care Units.Journal of clinical medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies have shown lipopolysaccharide from Gram-negative bacteria is cleared from the circulation via LDL receptors on hepatocytes, which are downregulated by PCSK9. Whether clearance of Gram positive bacterial lipoteichoic acid (LTA) shows similar dependence on PCSK9, and whether this is clinically relevant in Gram positive human sepsis, is unknown. We examined survival data from three cohorts of patients who had Gram positive septic shock (n = 170, n = 130, and n = 59) and found that patients who carried a PCSK9 loss-of-function (LOF) allele had significantly higher 28-day survival (73.8%) than those with no LOF alleles (52.8%) (p = 0.000038). Plasma clearance of LTA was also found to be increased in PCSK9 knockout mice compared to wildtype control mice (p = 0.002). In addition, hepatocytes pre-treated with recombinant wildtype PCSK9 showed a dose-dependent decrease in uptake of fluorescently-labeled LTA (p < 0.01). In comparison to wildtype PCSK9, hepatocytes pre-treated with 3 different LOF variants of recombinant PCSK9 showed an increase in LTA uptake. This study shows the clearance of LTA follows a similar route as lipopolysaccharide, which is dependent on hepatic LDL receptors. This has important implications in health as strategies aimed at inhibiting PCSK9 function may be an effective treatment option for both Gram-positive and negative sepsis.
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