Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification.

2.50
Hdl Handle:
http://hdl.handle.net/2336/620591
Title:
Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification.
Authors:
McGarrity, Sarah; Anuforo, Ósk; Halldórsson, Haraldur; Bergmann, Andreas; Halldórsson, Skarphéðinn; Palsson, Sirus; Henriksen, Hanne H; Johansson, Pär Ingemar; Rolfsson, Óttar
Citation:
Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification. 2018, 8 (1):6811 Sci Rep
Issue Date:
1-May-2018
Abstract:
Endothelial dysfunction contributes to sepsis outcome. Metabolic phenotypes associated with endothelial dysfunction are not well characterised in part due to difficulties in assessing endothelial metabolism in situ. Here, we describe the construction of iEC2812, a genome scale metabolic reconstruction of endothelial cells and its application to describe metabolic changes that occur following endothelial dysfunction. Metabolic gene expression analysis of three endothelial subtypes using iEC2812 suggested their similar metabolism in culture. To mimic endothelial dysfunction, an in vitro sepsis endothelial cell culture model was established and the metabotypes associated with increased endothelial permeability and glycocalyx loss after inflammatory stimuli were quantitatively defined through metabolomics. These data and transcriptomic data were then used to parametrize iEC2812 and investigate the metabotypes of endothelial dysfunction. Glycan production and increased fatty acid metabolism accompany increased glycocalyx shedding and endothelial permeability after inflammatory stimulation. iEC2812 was then used to analyse sepsis patient plasma metabolome profiles and predict changes to endothelial derived biomarkers. These analyses revealed increased changes in glycan metabolism in sepsis non-survivors corresponding to metabolism of endothelial dysfunction in culture. The results show concordance between endothelial health and sepsis survival in particular between endothelial cell metabolism and the plasma metabolome in patients with sepsis.
Description:
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files
Additional Links:
https://www.nature.com/articles/s41598-018-25015-5.pdf
Rights:
Archived with thanks to Scientific reports

Full metadata record

DC FieldValue Language
dc.contributor.authorMcGarrity, Sarahen
dc.contributor.authorAnuforo, Ósken
dc.contributor.authorHalldórsson, Haralduren
dc.contributor.authorBergmann, Andreasen
dc.contributor.authorHalldórsson, Skarphéðinnen
dc.contributor.authorPalsson, Sirusen
dc.contributor.authorHenriksen, Hanne Hen
dc.contributor.authorJohansson, Pär Ingemaren
dc.contributor.authorRolfsson, Óttaren
dc.date.accessioned2018-06-12T15:15:44Z-
dc.date.available2018-06-12T15:15:44Z-
dc.date.issued2018-05-01-
dc.date.submitted2018-
dc.identifier.citationMetabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification. 2018, 8 (1):6811 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid29717213-
dc.identifier.doi10.1038/s41598-018-25015-5-
dc.identifier.urihttp://hdl.handle.net/2336/620591-
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Filesen
dc.description.abstractEndothelial dysfunction contributes to sepsis outcome. Metabolic phenotypes associated with endothelial dysfunction are not well characterised in part due to difficulties in assessing endothelial metabolism in situ. Here, we describe the construction of iEC2812, a genome scale metabolic reconstruction of endothelial cells and its application to describe metabolic changes that occur following endothelial dysfunction. Metabolic gene expression analysis of three endothelial subtypes using iEC2812 suggested their similar metabolism in culture. To mimic endothelial dysfunction, an in vitro sepsis endothelial cell culture model was established and the metabotypes associated with increased endothelial permeability and glycocalyx loss after inflammatory stimuli were quantitatively defined through metabolomics. These data and transcriptomic data were then used to parametrize iEC2812 and investigate the metabotypes of endothelial dysfunction. Glycan production and increased fatty acid metabolism accompany increased glycocalyx shedding and endothelial permeability after inflammatory stimulation. iEC2812 was then used to analyse sepsis patient plasma metabolome profiles and predict changes to endothelial derived biomarkers. These analyses revealed increased changes in glycan metabolism in sepsis non-survivors corresponding to metabolism of endothelial dysfunction in culture. The results show concordance between endothelial health and sepsis survival in particular between endothelial cell metabolism and the plasma metabolome in patients with sepsis.en
dc.description.sponsorshipRANNIS Landspitali Reykjavik Rigshospitalet Copenhagenen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttps://www.nature.com/articles/s41598-018-25015-5.pdfen
dc.rightsArchived with thanks to Scientific reportsen
dc.subjectÆðasjúkdómaren
dc.subjectBlóðeitrunen
dc.subjectNAF12en
dc.subject.meshEndothelium, Vascularen
dc.subject.meshSepsisen
dc.titleMetabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification.en
dc.typeArticleen
dc.contributor.department[ 1 ] Univ Iceland, Ctr Syst Biol, Sturlugata 8, Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Med Dept, Sturlugata 8, Reykjavik, Iceland [ 3 ] Landspitali, Reykjavik, Iceland [ 4 ] Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen O, Denmarken
dc.identifier.journalScientific reportsen
dc.rights.accessOpen Access - Opinn aðganguren
dc.departmentcodeNAF12-

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