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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Autores principales:	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
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4cd3268817e5479b98ec5af3e90d7538
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spelling	oai:doaj.org-article:4cd3268817e5479b98ec5af3e90d75382021-12-02T15:53:02ZDetecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry10.1038/s41598-021-84523-z2045-2322https://doaj.org/article/4cd3268817e5479b98ec5af3e90d75382021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84523-zhttps://doaj.org/toc/2045-2322Abstract 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.Aleksandra Aljakna KhanNasim BararpourMarie GorkaTimothée JoyeSandrine MorelChristophe A. MontessuitSilke GrabherrTony FracassoMarc AugsburgerBrenda R. KwakAurélien ThomasSara SabatassoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
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 Portfolio
publishDate	2021
url	https://doaj.org/article/4cd3268817e5479b98ec5af3e90d7538
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Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry

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