Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry
Abstract Diagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6–12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a pa...
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doaj-4cd3268817e5479b98ec5af3e90d75382021-03-11T12:18:17ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111210.1038/s41598-021-84523-zDetecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometryAleksandra Aljakna Khan0Nasim Bararpour1Marie Gorka2Timothée Joye3Sandrine Morel4Christophe A. Montessuit5Silke Grabherr6Tony Fracasso7Marc Augsburger8Brenda R. Kwak9Aurélien Thomas10Sara Sabatasso11University Centre of Legal Medicine, Lausanne-GenevaUniversity Centre of Legal Medicine, Lausanne-GenevaEcole Des Sciences Criminelles/School of Criminal Justice, Faculty of Law, Criminal Justice, and Public Administration, University of LausanneUniversity Centre of Legal Medicine, Lausanne-GenevaDepartment of Pathology and Immunology, University of GenevaDepartment of Pathology and Immunology, University of GenevaUniversity Centre of Legal Medicine, Lausanne-GenevaUniversity Centre of Legal Medicine, Lausanne-GenevaUniversity Centre of Legal Medicine, Lausanne-GenevaDepartment of Pathology and Immunology, University of GenevaUniversity Centre of Legal Medicine, Lausanne-GenevaUniversity Centre of Legal Medicine, Lausanne-GenevaAbstract Diagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6–12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a panel of molecular tissue markers is a promising approach and can be accelerated by characterization of molecular changes. This study is the first untargeted metabolomic profiling of ischemic myocardium during the initial 4 h directly from tissue section. Ischemic hearts from an ex-vivo Langendorff model were analysed using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) at 15 min, 30 min, 1 h, 2 h, and 4 h. Region-specific molecular changes were identified even in absence of evident histological lesions and were segregated by unsupervised cluster analysis. Significantly differentially expressed features were detected by multivariate analysis starting at 15 min while their number increased with prolonged ischemia. The biggest significant increase at 15 min was observed for m/z 682.1294 (likely corresponding to S-NADHX—a damage product of nicotinamide adenine dinucleotide (NADH)). Based on the previously reported role of NAD+/NADH ratio in regulating localization of the sodium channel (Nav1.5) at the plasma membrane, Nav1.5 was evaluated by immunofluorescence. As expected, a fainter signal was observed at the plasma membrane in the predicted ischemic region starting 30 min of ischemia and the change became the most pronounced by 4 h. Metabolomic changes occur early during ischemia, can assist in identifying markers for post-mortem diagnostics and improve understanding of molecular mechanisms.https://doi.org/10.1038/s41598-021-84523-z |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aleksandra Aljakna Khan Nasim Bararpour Marie Gorka Timothée Joye Sandrine Morel Christophe A. Montessuit Silke Grabherr Tony Fracasso Marc Augsburger Brenda R. Kwak Aurélien Thomas Sara Sabatasso |
spellingShingle |
Aleksandra Aljakna Khan Nasim Bararpour Marie Gorka Timothée Joye Sandrine Morel Christophe A. Montessuit Silke Grabherr Tony Fracasso Marc Augsburger Brenda R. Kwak Aurélien Thomas Sara Sabatasso Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry Scientific Reports |
author_facet |
Aleksandra Aljakna Khan Nasim Bararpour Marie Gorka Timothée Joye Sandrine Morel Christophe A. Montessuit Silke Grabherr Tony Fracasso Marc Augsburger Brenda R. Kwak Aurélien Thomas Sara Sabatasso |
author_sort |
Aleksandra Aljakna Khan |
title |
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry |
title_short |
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry |
title_full |
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry |
title_fullStr |
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry |
title_full_unstemmed |
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry |
title_sort |
detecting early myocardial ischemia in rat heart by maldi imaging mass spectrometry |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
Abstract Diagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6–12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a panel of molecular tissue markers is a promising approach and can be accelerated by characterization of molecular changes. This study is the first untargeted metabolomic profiling of ischemic myocardium during the initial 4 h directly from tissue section. Ischemic hearts from an ex-vivo Langendorff model were analysed using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) at 15 min, 30 min, 1 h, 2 h, and 4 h. Region-specific molecular changes were identified even in absence of evident histological lesions and were segregated by unsupervised cluster analysis. Significantly differentially expressed features were detected by multivariate analysis starting at 15 min while their number increased with prolonged ischemia. The biggest significant increase at 15 min was observed for m/z 682.1294 (likely corresponding to S-NADHX—a damage product of nicotinamide adenine dinucleotide (NADH)). Based on the previously reported role of NAD+/NADH ratio in regulating localization of the sodium channel (Nav1.5) at the plasma membrane, Nav1.5 was evaluated by immunofluorescence. As expected, a fainter signal was observed at the plasma membrane in the predicted ischemic region starting 30 min of ischemia and the change became the most pronounced by 4 h. Metabolomic changes occur early during ischemia, can assist in identifying markers for post-mortem diagnostics and improve understanding of molecular mechanisms. |
url |
https://doi.org/10.1038/s41598-021-84523-z |
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