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Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry
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 mo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933419/ https://www.ncbi.nlm.nih.gov/pubmed/33664384 http://dx.doi.org/10.1038/s41598-021-84523-z |
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author | Aljakna Khan, Aleksandra Bararpour, Nasim Gorka, Marie Joye, Timothée Morel, Sandrine Montessuit, Christophe A. Grabherr, Silke Fracasso, Tony Augsburger, Marc Kwak, Brenda R. Thomas, Aurélien Sabatasso, Sara |
author_facet | Aljakna Khan, Aleksandra Bararpour, Nasim Gorka, Marie Joye, Timothée Morel, Sandrine Montessuit, Christophe A. Grabherr, Silke Fracasso, Tony Augsburger, Marc Kwak, Brenda R. Thomas, Aurélien Sabatasso, Sara |
author_sort | Aljakna Khan, Aleksandra |
collection | PubMed |
description | 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 (Na(v)1.5) at the plasma membrane, Na(v)1.5 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. |
format | Online Article Text |
id | pubmed-7933419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79334192021-03-08 Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry Aljakna Khan, Aleksandra Bararpour, Nasim Gorka, Marie Joye, Timothée Morel, Sandrine Montessuit, Christophe A. Grabherr, Silke Fracasso, Tony Augsburger, Marc Kwak, Brenda R. Thomas, Aurélien Sabatasso, Sara Sci Rep Article 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 (Na(v)1.5) at the plasma membrane, Na(v)1.5 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. Nature Publishing Group UK 2021-03-04 /pmc/articles/PMC7933419/ /pubmed/33664384 http://dx.doi.org/10.1038/s41598-021-84523-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Aljakna Khan, Aleksandra Bararpour, Nasim Gorka, Marie Joye, Timothée Morel, Sandrine Montessuit, Christophe A. Grabherr, Silke Fracasso, Tony Augsburger, Marc Kwak, Brenda R. Thomas, Aurélien Sabatasso, Sara Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933419/ https://www.ncbi.nlm.nih.gov/pubmed/33664384 http://dx.doi.org/10.1038/s41598-021-84523-z |
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