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

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 rec...

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Autores principales:	Sarah McGarrity, Ósk Anuforo, Haraldur Halldórsson, Andreas Bergmann, Skarphéðinn Halldórsson, Sirus Palsson, Hanne H. Henriksen, Pär Ingemar Johansson, Óttar Rolfsson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3346a06d5da14fb4a956f403770503f3
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spelling	oai:doaj.org-article:3346a06d5da14fb4a956f403770503f32021-12-02T15:09:10ZMetabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification10.1038/s41598-018-25015-52045-2322https://doaj.org/article/3346a06d5da14fb4a956f403770503f32018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25015-5https://doaj.org/toc/2045-2322Abstract 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.Sarah McGarrityÓsk AnuforoHaraldur HalldórssonAndreas BergmannSkarphéðinn HalldórssonSirus PalssonHanne H. HenriksenPär Ingemar JohanssonÓttar RolfssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah McGarrity Ósk Anuforo Haraldur Halldórsson Andreas Bergmann Skarphéðinn Halldórsson Sirus Palsson Hanne H. Henriksen Pär Ingemar Johansson Óttar Rolfsson Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
description	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.
format	article
author	Sarah McGarrity Ósk Anuforo Haraldur Halldórsson Andreas Bergmann Skarphéðinn Halldórsson Sirus Palsson Hanne H. Henriksen Pär Ingemar Johansson Óttar Rolfsson
author_facet	Sarah McGarrity Ósk Anuforo Haraldur Halldórsson Andreas Bergmann Skarphéðinn Halldórsson Sirus Palsson Hanne H. Henriksen Pär Ingemar Johansson Óttar Rolfsson
author_sort	Sarah McGarrity
title	Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
title_short	Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
title_full	Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
title_fullStr	Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
title_full_unstemmed	Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
title_sort	metabolic systems analysis of lps induced endothelial dysfunction applied to sepsis patient stratification
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3346a06d5da14fb4a956f403770503f3
work_keys_str_mv	AT sarahmcgarrity metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT oskanuforo metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT haraldurhalldorsson metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT andreasbergmann metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT skarpheðinnhalldorsson metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT siruspalsson metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT hannehhenriksen metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT paringemarjohansson metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification AT ottarrolfsson metabolicsystemsanalysisoflpsinducedendothelialdysfunctionappliedtosepsispatientstratification
_version_	1718387865968181248

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

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