Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis
Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 September 2020
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| In: |
Scientific reports
Year: 2020, Volume: 10 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-71870-6 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41598-020-71870-6 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41598-020-71870-6 
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| Author Notes: | Martin Mollenhauer, Dennis Mehrkens, Anna Klinke, Max Lange, Lisa Remane, Kai Friedrichs, Simon Braumann, Simon Geißen, Sakine Simsekyilmaz, Felix S. Nettersheim, Samuel Lee, Gabriel Peinkofer, Anne C. Geisler, Bianca Geis, Alexander P. Schwoerer, Lucie Carrier, Bruce A. Freeman, Matthias Dewenter, Xiaojing Luo, Ali El-Armouche, Michael Wagner, Matti Adam, Stephan Baldus & Volker Rudolph |
| Summary: | Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development. |
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| Item Description: | Gesehen am 26.10.2021 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-71870-6 |