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Host Response and Inflammation

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Not Induced in Artificial Human Inflammation and Is Not Correlated with Inflammatory Response

Matthias Wolfgang Heinzl, Michael Resl, Carmen Klammer, Margot Egger, Benjamin Dieplinger, Martin Clodi
Manuela Raffatellu, Editor
Matthias Wolfgang Heinzl
aDepartment of Internal Medicine, Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Linz, Austria
cICMR–Institute for Cardiovascular and Metabolic Research, JKU Linz, Linz, Austria
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  • ORCID record for Matthias Wolfgang Heinzl
Michael Resl
aDepartment of Internal Medicine, Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Linz, Austria
cICMR–Institute for Cardiovascular and Metabolic Research, JKU Linz, Linz, Austria
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Carmen Klammer
aDepartment of Internal Medicine, Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Linz, Austria
cICMR–Institute for Cardiovascular and Metabolic Research, JKU Linz, Linz, Austria
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Margot Egger
bDepartment of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Linz, Austria
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Benjamin Dieplinger
bDepartment of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Linz, Austria
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Martin Clodi
aDepartment of Internal Medicine, Konventhospital Barmherzige Brueder Linz (St. John of God Hospital Linz), Linz, Austria
cICMR–Institute for Cardiovascular and Metabolic Research, JKU Linz, Linz, Austria
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Manuela Raffatellu
University of California San Diego School of Medicine
Roles: Editor
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DOI: 10.1128/IAI.00842-19
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  • FIG 1
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    FIG 1

    Mean plasma concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP). The difference between placebo and LPS administration was statistically significant for IL-6 (P = 0.018) as well as CRP (P < 0.001), as measured by RM-ANOVA. IL-6 values are given in picograms per milliliter on the lefthand side; the assay’s upper limit of normal is 15 pg/ml. CRP values are given in milligrams per deciliter on the righthand side; the assay’s upper limit of normal is 1.0 mg/dl.

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    FIG 2

    RM-ANOVA for PCSK9. There was no statistically significant difference in PCSK9 plasma concentrations between placebo and LPS administration (P = 0.44 using the Greenhouse-Geisser correction). Time points are shown on the abscissa, and plasma concentrations of PCSK9 are shown on the ordinate (values given in nanograms per milliliter). Error bars depict 95% confidence intervals. The decrease of PCSK9 throughout the study day is due to fasting conditions and diurnal variation (26).

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    FIG 3

    RM-ANOVA for LDL. The difference in LDL plasma concentrations between placebo and LPS administration was statistically significant (P < 0.001 using the Greenhouse-Geisser correction). Time points are shown on the abscissa, the ratio of LDL values to baseline is shown on the ordinate. Error bars depict 95% confidence intervals. Of note, there was a distinct peak in LDL levels 60 min after LPS administration. This relative elevation of LDL levels following LPS infusion was not statistically significant after correction for baseline difference (P = 0.065 using the Greenhouse-Geisser correction).

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    FIG 4

    Scatter plot depicting the negative correlation between LDL levels at baseline and IL-6 levels 24 h after the administration of LPS. This negative correlation was statistically significant (Pearson coefficient of correlation = −0.699; P = 0.024).

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  • TABLE 1

    Correlations between lipid parameters at baseline and IL-6 as a marker of inflammation after LPS infusionb

    TABLE 1
    • ↵a P values were determined by two-tailed test. Abbreviations: ApoA1, apolipoprotein A-I; ApoB, apolipoprotein B; Lp(a), lipoprotein (a).

    • ↵b There was a significant correlation between LDL and IL-6 at 24 h after LPS infusion. HDL and ApoA1 show significant correlations with IL-6 at both 360 min and 24 h after LPS infusion. For PCSK9 as well as ApoB, there was no significant correlation with markers of inflammation. All baseline values were measured before LPS administration.

  • TABLE 2

    Correlations between inflammatory markers and the course of LDL/HDL as calculated by the change ratioa

    TABLE 2
    • ↵a To illustrate the course of LDL and HDL levels after LPS administration relative to placebo, a change ratio was calculated by dividing the ratio of a value at a given time point after LPS administration to baseline by the same ratio following placebo. The degree of the decrease of neither LDL nor HDL, as calculated by the change ratio, correlated with either marker of inflammation. The change ratio at 60 min as a calculated number depicting the relative, nonsignificant peak of LDL and HDL at this time point correlated significantly with IL-6 levels at 360 min after LPS. In the case of LDL, there was also a significant correlation with IL-6 at 180 min (P = 0.031) as well as with CRP levels at 360 min (P = 0.049), 24 h (P = 0.012), and 48 h (P = 0.022) after LPS infusion. All correlations between inflammatory markers and change ratios at 60 min after LPS infusion were positive.

    • ↵b P values were determined by two-tailed test.

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      Tables S1 to S3; Fig. S1 to S7

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Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Not Induced in Artificial Human Inflammation and Is Not Correlated with Inflammatory Response
Matthias Wolfgang Heinzl, Michael Resl, Carmen Klammer, Margot Egger, Benjamin Dieplinger, Martin Clodi
Infection and Immunity Feb 2020, 88 (3) e00842-19; DOI: 10.1128/IAI.00842-19

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Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Not Induced in Artificial Human Inflammation and Is Not Correlated with Inflammatory Response
Matthias Wolfgang Heinzl, Michael Resl, Carmen Klammer, Margot Egger, Benjamin Dieplinger, Martin Clodi
Infection and Immunity Feb 2020, 88 (3) e00842-19; DOI: 10.1128/IAI.00842-19
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    • ABSTRACT
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KEYWORDS

proprotein convertase subtilisin/kexin type 9
PCSK9
pathogen lipids
low-density lipoprotein
LDL
inflammation
lipopolysaccharide
LPS
human endotoxin model

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