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Elevated plasma glypicans are associated with organ failure in patients with infection

Fisher, Jane LU ; Linder, Adam LU and Bentzer, Peter LU (2019) In Intensive Care Medicine Experimental 7.
Abstract
Background
Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. We hypothesized that plasma levels of glypicans (GPC) are elevated in patients with sepsis.

Methods
Plasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening. Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection. Patients were divided into groups of those who had sepsis and those who had an... (More)
Background
Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. We hypothesized that plasma levels of glypicans (GPC) are elevated in patients with sepsis.

Methods
Plasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening. Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection. Patients were divided into groups of those who had sepsis and those who had an infection without organ failure. To determine whether plasma glypicans could predict the development of organ failure, patients were further subdivided to those who had organ failure at enrolment and those who developed it after enrollment. The association of plasma GPC 1, 3, and 4 with organ failure and with various markers of inflammation, disease severity, and glycocalyx shedding was investigated.

Results
In the pilot study, only GPC 1, 3, and 4 were detectable in the plasma of sepsis patients. In the larger cohort, GPC 1, 3, and 4 levels were significantly higher (p < 0.001) in patients with sepsis than in those with infection without organ failure. GPC 1, 3, and 4 were significantly positively correlated with plasma levels of the disease severity markers C-reactive protein, lactate, procalcitonin, and heparin binding protein, and with the marker of glycocalyx degradation syndecan 1. They were significantly negatively correlated with plasma levels of the glycocalyx-protective factors apolipoprotein M and sphingosine-1-phosphate.

Conclusions
We show that GPC 1, 3, and 4 are elevated in plasma of patients with sepsis and correlate with markers of disease severity, systemic inflammation, and glycocalyx damage. (Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Intensive Care Medicine Experimental
volume
7
article number
2
publisher
Springer
external identifiers
  • pmid:30618011
  • scopus:85071115140
ISSN
2197-425X
DOI
10.1186/s40635-018-0216-z
language
English
LU publication?
yes
id
17cbaa7d-f980-4288-904a-7839285123eb
date added to LUP
2020-08-14 11:03:32
date last changed
2022-06-30 04:18:25
@article{17cbaa7d-f980-4288-904a-7839285123eb,
  abstract     = {{Background<br>
Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. We hypothesized that plasma levels of glypicans (GPC) are elevated in patients with sepsis.<br>
<br>
Methods<br>
Plasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening. Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection. Patients were divided into groups of those who had sepsis and those who had an infection without organ failure. To determine whether plasma glypicans could predict the development of organ failure, patients were further subdivided to those who had organ failure at enrolment and those who developed it after enrollment. The association of plasma GPC 1, 3, and 4 with organ failure and with various markers of inflammation, disease severity, and glycocalyx shedding was investigated.<br>
<br>
Results<br>
In the pilot study, only GPC 1, 3, and 4 were detectable in the plasma of sepsis patients. In the larger cohort, GPC 1, 3, and 4 levels were significantly higher (p &lt; 0.001) in patients with sepsis than in those with infection without organ failure. GPC 1, 3, and 4 were significantly positively correlated with plasma levels of the disease severity markers C-reactive protein, lactate, procalcitonin, and heparin binding protein, and with the marker of glycocalyx degradation syndecan 1. They were significantly negatively correlated with plasma levels of the glycocalyx-protective factors apolipoprotein M and sphingosine-1-phosphate.<br>
<br>
Conclusions<br>
We show that GPC 1, 3, and 4 are elevated in plasma of patients with sepsis and correlate with markers of disease severity, systemic inflammation, and glycocalyx damage.}},
  author       = {{Fisher, Jane and Linder, Adam and Bentzer, Peter}},
  issn         = {{2197-425X}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Intensive Care Medicine Experimental}},
  title        = {{Elevated plasma glypicans are associated with organ failure in patients with infection}},
  url          = {{http://dx.doi.org/10.1186/s40635-018-0216-z}},
  doi          = {{10.1186/s40635-018-0216-z}},
  volume       = {{7}},
  year         = {{2019}},
}