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Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

Introduction Acute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This st...

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Published in:Metabolomics 2021-09, Vol.17 (9), p.76-76, Article 76
Main Authors: Chacko, Sanoj, Mamas, Mamas A., El-Omar, Magdi, Simon, David, Haseeb, Sohaib, Fath-ordoubadi, Farzin, Clarke, Bernard, Neyses, Ludwig, Dunn, Warwick B.
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creator Chacko, Sanoj
Mamas, Mamas A.
El-Omar, Magdi
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Fath-ordoubadi, Farzin
Clarke, Bernard
Neyses, Ludwig
Dunn, Warwick B.
description Introduction Acute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. Methods Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. Results The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P 
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Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. Methods Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. Results The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P &lt; 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important. Conclusion Using an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.</description><identifier>ISSN: 1573-3882</identifier><identifier>EISSN: 1573-3890</identifier><identifier>DOI: 10.1007/s11306-021-01827-x</identifier><identifier>PMID: 34424431</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Anaerobic respiration ; Arachidonic acid ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Coronary Artery Disease ; Coronary Occlusion ; Developmental Biology ; Docosahexaenoic acid ; Heart ; Humans ; Ischemia ; Life Sciences ; Liquid chromatography ; Mass spectroscopy ; Metabolism ; Metabolites ; Metabolome ; Metabolomics ; Molecular Medicine ; Occlusion ; Original ; Original Article ; Oxidation ; Percutaneous Coronary Intervention ; Sphingosine 1-phosphate ; Tryptophan</subject><ispartof>Metabolomics, 2021-09, Vol.17 (9), p.76-76, Article 76</ispartof><rights>Crown 2021</rights><rights>2021. Crown.</rights><rights>Crown 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-a9b33bd7196f62601435bf20f3bebe19ec34ea27fb3b434cf3aa12da4de135ad3</citedby><cites>FETCH-LOGICAL-c474t-a9b33bd7196f62601435bf20f3bebe19ec34ea27fb3b434cf3aa12da4de135ad3</cites><orcidid>0000-0003-1699-6247</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34424431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chacko, Sanoj</creatorcontrib><creatorcontrib>Mamas, Mamas A.</creatorcontrib><creatorcontrib>El-Omar, Magdi</creatorcontrib><creatorcontrib>Simon, David</creatorcontrib><creatorcontrib>Haseeb, Sohaib</creatorcontrib><creatorcontrib>Fath-ordoubadi, Farzin</creatorcontrib><creatorcontrib>Clarke, Bernard</creatorcontrib><creatorcontrib>Neyses, Ludwig</creatorcontrib><creatorcontrib>Dunn, Warwick B.</creatorcontrib><title>Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia</title><title>Metabolomics</title><addtitle>Metabolomics</addtitle><addtitle>Metabolomics</addtitle><description>Introduction Acute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. Methods Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. Results The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P &lt; 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important. Conclusion Using an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. 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Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale. Objectives This study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach. Methods Peripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach. Results The study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P &lt; 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important. Conclusion Using an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34424431</pmid><doi>10.1007/s11306-021-01827-x</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-1699-6247</orcidid><oa>free_for_read</oa></addata></record>
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subjects Anaerobic respiration
Arachidonic acid
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Coronary Artery Disease
Coronary Occlusion
Developmental Biology
Docosahexaenoic acid
Heart
Humans
Ischemia
Life Sciences
Liquid chromatography
Mass spectroscopy
Metabolism
Metabolites
Metabolome
Metabolomics
Molecular Medicine
Occlusion
Original
Original Article
Oxidation
Percutaneous Coronary Intervention
Sphingosine 1-phosphate
Tryptophan
title Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia
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