Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids

Abstract The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsi...

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Main Authors: Dawoud Sulaiman, Dongyuan Wu, Lauren Page Black, Kevin J. Williams, Kiley Graim, Susmita Datta, Srinivasa T. Reddy, Faheem W. Guirgis
Format: Article
Language:English
Published: Wiley 2024-03-01
Series:Clinical and Translational Science
Online Access:https://doi.org/10.1111/cts.13745
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author Dawoud Sulaiman
Dongyuan Wu
Lauren Page Black
Kevin J. Williams
Kiley Graim
Susmita Datta
Srinivasa T. Reddy
Faheem W. Guirgis
author_facet Dawoud Sulaiman
Dongyuan Wu
Lauren Page Black
Kevin J. Williams
Kiley Graim
Susmita Datta
Srinivasa T. Reddy
Faheem W. Guirgis
author_sort Dawoud Sulaiman
collection DOAJ
description Abstract The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis‐3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid‐chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro‐inflammatory signaling lipids from ω‐6 poly‐unsaturated fatty acids (PUFAs), including 15‐hydroxyeicosatetraenoic (HETE), 12‐HETE, and 11‐HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro‐resolving lipid mediator from ω‐3 PUFAs, 14(S)‐hydroxy docosahexaenoic acid (14S‐HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor‐outcome patients with sepsis and may serve as targets for future therapies.
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spelling doaj.art-34b08e111f7b43588b4cdc74d37880692024-03-26T04:50:33ZengWileyClinical and Translational Science1752-80541752-80622024-03-01173n/an/a10.1111/cts.13745Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipidsDawoud Sulaiman0Dongyuan Wu1Lauren Page Black2Kevin J. Williams3Kiley Graim4Susmita Datta5Srinivasa T. Reddy6Faheem W. Guirgis7Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles California USADepartment of Biostatistics University of Florida Gainesville Florida USADepartment of Emergency Medicine Northwestern University Chicago IL USADepartment of Biological Chemistry David Geffen School of Medicine at UCLA Los Angeles California USAComputer and Information Science and Engineering University of Florida Gainesville Florida USADepartment of Biostatistics University of Florida Gainesville Florida USADivision of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles California USADepartment of Emergency Medicine University of Florida College of Medicine Gainesville Florida USAAbstract The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis‐3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid‐chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro‐inflammatory signaling lipids from ω‐6 poly‐unsaturated fatty acids (PUFAs), including 15‐hydroxyeicosatetraenoic (HETE), 12‐HETE, and 11‐HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro‐resolving lipid mediator from ω‐3 PUFAs, 14(S)‐hydroxy docosahexaenoic acid (14S‐HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor‐outcome patients with sepsis and may serve as targets for future therapies.https://doi.org/10.1111/cts.13745
spellingShingle Dawoud Sulaiman
Dongyuan Wu
Lauren Page Black
Kevin J. Williams
Kiley Graim
Susmita Datta
Srinivasa T. Reddy
Faheem W. Guirgis
Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids
Clinical and Translational Science
title Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids
title_full Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids
title_fullStr Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids
title_full_unstemmed Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids
title_short Lipidomic changes in a novel sepsis outcome‐based analysis reveals potent pro‐inflammatory and pro‐resolving signaling lipids
title_sort lipidomic changes in a novel sepsis outcome based analysis reveals potent pro inflammatory and pro resolving signaling lipids
url https://doi.org/10.1111/cts.13745
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