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Infect Immun. 2019 Dec 16. pii: IAI.00842-19. doi: 10.1128/IAI.00842-19. [Epub ahead of print]

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is not induced in artificial human inflammation and is not correlated with inflammatory response.

Author information

1
Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Austria, Department of Internal Medicine, (MW.H., M.R., C.K., M.C.) and Department of Laboratory Medicine (M.E., B.D.,) ICMR - Institute for Cardiovascular and Metabolic Research, JKU Linz, Austria (M.H., M.R., C.K., M.C.).
2
Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Austria, Department of Internal Medicine, (MW.H., M.R., C.K., M.C.) and Department of Laboratory Medicine (M.E., B.D.,) ICMR - Institute for Cardiovascular and Metabolic Research, JKU Linz, Austria (M.H., M.R., C.K., M.C.) martin.clodi@bblinz.at.

Abstract

Background: Lipoproteins as well as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) have been shown to play a key role in the innate immune response. However, knowledge about the role and kinetics of PCSK9 in human inflammation is currently insufficient. The aim of this study was to investigate the interaction between inflammation and lipid metabolism including the possible role of PCSK9.Methods: A single-blinded, placebo-controlled cross-over study using the Human Endotoxin Model was performed. Ten healthy men received lipopolysaccharide (LPS) or placebo on two different study days after overnight fasting. Lipoproteins as well as PCSK9 were measured repetitively over 48 hours.Results: PCSK9 plasma concentrations were not induced by LPS infusion and no correlation between PCSK9 plasma concentrations and the degree of inflammation could be identified. The observed LDL response to inflammation was more complex than anticipated, especially in the very early phase after the inflammatory stimulus. Baseline concentrations of LDL as well as HDL correlated negatively with inflammatory response.Conclusions: Our data suggest that the lipoprotein response to inflammation seems to be independent of PCSK9. The proposed elevations of PCSK9 and suspected correlations between PCSK9 levels and inflammatory response are not supported by our data.Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT03392701.

PMID:
31843964
DOI:
10.1128/IAI.00842-19
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