The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model
Ventricular arrhythmias associated with myocardial infarction (MI) have a significant impact on mortality in patients following heart attack. Therefore, targeted reduction of arrhythmia represents a therapeutic approach for the prevention and treatment of severe events after infarction. Recent resea...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8843 |
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| author | Beschan Ahmad Anna Skorska Markus Wolfien Haval Sadraddin Heiko Lemcke Praveen Vasudevan Olaf Wolkenhauer Gustav Steinhoff Robert David Ralf Gaebel |
| author_facet | Beschan Ahmad Anna Skorska Markus Wolfien Haval Sadraddin Heiko Lemcke Praveen Vasudevan Olaf Wolkenhauer Gustav Steinhoff Robert David Ralf Gaebel |
| author_sort | Beschan Ahmad |
| collection | DOAJ |
| description | Ventricular arrhythmias associated with myocardial infarction (MI) have a significant impact on mortality in patients following heart attack. Therefore, targeted reduction of arrhythmia represents a therapeutic approach for the prevention and treatment of severe events after infarction. Recent research transplanting mesenchymal stem cells (MSC) showed their potential in MI therapy. Our study aimed to investigate the effects of MSC injection on post-infarction arrhythmia. We used our murine double infarction model, which we previously established, to more closely mimic the clinical situation and intramyocardially injected hypoxic pre-conditioned murine MSC to the infarction border. Thereafter, various types of arrhythmias were recorded and analyzed. We observed a homogenous distribution of all types of arrhythmias after the first infarction, without any significant differences between the groups. Yet, MSC therapy after double infarction led to a highly significant reduction in simple and complex arrhythmias. Moreover, RNA-sequencing of samples from stem cell treated mice after re-infarction demonstrated a significant decline in most arrhythmias with reduced inflammatory pathways. Additionally, following stem-cell therapy we found numerous highly expressed genes to be either linked to lowering the risk of heart failure, cardiomyopathy or sudden cardiac death. Moreover, genes known to be associated with arrhythmogenesis and key mutations underlying arrhythmias were downregulated. In summary, our stem-cell therapy led to a reduction in cardiac arrhythmias after MI and showed a downregulation of already established inflammatory pathways. Furthermore, our study reveals gene regulation pathways that have a potentially direct influence on arrhythmogenesis after myocardial infarction. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:22:27Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f0ab944d528f43138dac8a0667cc296c2023-12-03T13:46:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316884310.3390/ijms23168843The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse ModelBeschan Ahmad0Anna Skorska1Markus Wolfien2Haval Sadraddin3Heiko Lemcke4Praveen Vasudevan5Olaf Wolkenhauer6Gustav Steinhoff7Robert David8Ralf Gaebel9Department of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Systems Biology and Bioinformatics, University of Rostock, 18051 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Rostock University Medical Center, 18057 Rostock, GermanyVentricular arrhythmias associated with myocardial infarction (MI) have a significant impact on mortality in patients following heart attack. Therefore, targeted reduction of arrhythmia represents a therapeutic approach for the prevention and treatment of severe events after infarction. Recent research transplanting mesenchymal stem cells (MSC) showed their potential in MI therapy. Our study aimed to investigate the effects of MSC injection on post-infarction arrhythmia. We used our murine double infarction model, which we previously established, to more closely mimic the clinical situation and intramyocardially injected hypoxic pre-conditioned murine MSC to the infarction border. Thereafter, various types of arrhythmias were recorded and analyzed. We observed a homogenous distribution of all types of arrhythmias after the first infarction, without any significant differences between the groups. Yet, MSC therapy after double infarction led to a highly significant reduction in simple and complex arrhythmias. Moreover, RNA-sequencing of samples from stem cell treated mice after re-infarction demonstrated a significant decline in most arrhythmias with reduced inflammatory pathways. Additionally, following stem-cell therapy we found numerous highly expressed genes to be either linked to lowering the risk of heart failure, cardiomyopathy or sudden cardiac death. Moreover, genes known to be associated with arrhythmogenesis and key mutations underlying arrhythmias were downregulated. In summary, our stem-cell therapy led to a reduction in cardiac arrhythmias after MI and showed a downregulation of already established inflammatory pathways. Furthermore, our study reveals gene regulation pathways that have a potentially direct influence on arrhythmogenesis after myocardial infarction.https://www.mdpi.com/1422-0067/23/16/8843mesenchymal stem cellsmyocardial infarctioncalcium regulationventricular arrhythmiahypoxic precondition |
| spellingShingle | Beschan Ahmad Anna Skorska Markus Wolfien Haval Sadraddin Heiko Lemcke Praveen Vasudevan Olaf Wolkenhauer Gustav Steinhoff Robert David Ralf Gaebel The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model International Journal of Molecular Sciences mesenchymal stem cells myocardial infarction calcium regulation ventricular arrhythmia hypoxic precondition |
| title | The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model |
| title_full | The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model |
| title_fullStr | The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model |
| title_full_unstemmed | The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model |
| title_short | The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model |
| title_sort | effects of hypoxic preconditioned murine mesenchymal stem cells on post infarct arrhythmias in the mouse model |
| topic | mesenchymal stem cells myocardial infarction calcium regulation ventricular arrhythmia hypoxic precondition |
| url | https://www.mdpi.com/1422-0067/23/16/8843 |
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