Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry
| Autor: | Timothée Joye, Christophe Albert Montessuit, Tony Fracasso, Marc Augsburger, Sara Sabatasso, Silke Grabherr, Brenda R. Kwak, Sandrine Morel, Aleksandra Aljakna Khan, Marie Gorka, Nasim Bararpour, Aurélien Thomas |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MALDI imaging Pathology medicine.medical_specialty Time Factors Science Ischemia Myocardial Infarction Myocardial Ischemia Coronary Artery Disease ddc:616.07 030204 cardiovascular system & hematology Nicotinamide adenine dinucleotide Mass spectrometry imaging Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics medicine Animals Humans Myocardial infarction Multidisciplinary Cardiovascular models Mass spectrometry Sodium channel Myocardium ddc:614.1 High-throughput screening Diagnostic markers Heart medicine.disease NAD Rats Autopsy Coronary Artery Disease/diagnosis Coronary Artery Disease/diagnostic imaging Coronary Artery Disease/metabolism Coronary Artery Disease/pathology Heart/diagnostic imaging Myocardial Ischemia/diagnosis Myocardial Ischemia/diagnostic imaging Myocardial Ischemia/metabolism Myocardial Ischemia/pathology Myocardium/metabolism Myocardium/pathology NAD/isolation & purification NAD/metabolism Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization 030104 developmental biology chemistry Medicine NAD+ kinase |
| Zdroj: | Scientific Reports Scientific reports, vol. 11, no. 1, pp. 5135 Scientific Reports, Vol. 11, No 1 (2021) P. 5135 Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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