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Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm

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Henriksen, HH, McGarrity, S, SigurÐardóttir, RS, Nemkov, T, D'Alessandro, A, Palsson, BO, Stensballe, J, Wade, CE, Rolfsson, Ó & Johansson, PI 2020, 'Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm' Annals of Surgery, bind 272, nr. 6, s. 1140-1148. https://doi.org/10.1097/SLA.0000000000003307

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Henriksen, Hanne H ; McGarrity, Sarah ; SigurÐardóttir, Rósa S ; Nemkov, Travis ; D'Alessandro, Angelo ; Palsson, Bernhard O ; Stensballe, Jakob ; Wade, Charles E ; Rolfsson, Óttar ; Johansson, Pär I. / Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma : A New Research Paradigm. I: Annals of Surgery. 2020 ; Bind 272, Nr. 6. s. 1140-1148.

Bibtex

@article{6ddf71368a2c4c8da5f699c76d06a554,
title = "Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm",
abstract = "OBJECTIVE: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma.BACKGROUND: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1.METHODS: Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function.RESULTS: Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1).CONCLUSIONS: We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.",
author = "Henriksen, {Hanne H} and Sarah McGarrity and Sigur{\DH}ard{\'o}ttir, {R{\'o}sa S} and Travis Nemkov and Angelo D'Alessandro and Palsson, {Bernhard O} and Jakob Stensballe and Wade, {Charles E} and {\'O}ttar Rolfsson and Johansson, {P{\"a}r I}",
year = "2020",
month = "12",
doi = "10.1097/SLA.0000000000003307",
language = "English",
volume = "272",
pages = "1140--1148",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams & Wilkins",
number = "6",

}

RIS

TY - JOUR

T1 - Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma

T2 - A New Research Paradigm

AU - Henriksen, Hanne H

AU - McGarrity, Sarah

AU - SigurÐardóttir, Rósa S

AU - Nemkov, Travis

AU - D'Alessandro, Angelo

AU - Palsson, Bernhard O

AU - Stensballe, Jakob

AU - Wade, Charles E

AU - Rolfsson, Óttar

AU - Johansson, Pär I

PY - 2020/12

Y1 - 2020/12

N2 - OBJECTIVE: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma.BACKGROUND: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1.METHODS: Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function.RESULTS: Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1).CONCLUSIONS: We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.

AB - OBJECTIVE: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma.BACKGROUND: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1.METHODS: Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function.RESULTS: Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1).CONCLUSIONS: We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.

U2 - 10.1097/SLA.0000000000003307

DO - 10.1097/SLA.0000000000003307

M3 - Journal article

VL - 272

SP - 1140

EP - 1148

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 6

ER -

ID: 57521770