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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Bibliographic Details
Published in:Scientific reports 2020-09, Vol.10 (1), p.15319, Article 15319
Main Authors: Mollenhauer, Martin, Mehrkens, Dennis, Klinke, Anna, Lange, Max, Remane, Lisa, Friedrichs, Kai, Braumann, Simon, Geißen, Simon, Simsekyilmaz, Sakine, Nettersheim, Felix S, Lee, Samuel, Peinkofer, Gabriel, Geisler, Anne C, Geis, Bianca, Schwoerer, Alexander P, Carrier, Lucie, Freeman, Bruce A, Dewenter, Matthias, Luo, Xiaojing, El-Armouche, Ali, Wagner, Michael, Adam, Matti, Baldus, Stephan, Rudolph, Volker
Format: Article
Language:English
Subjects:
Animals
Anti-Arrhythmia Agents - pharmacology
Arrhythmias, Cardiac - drug therapy
Arrhythmias, Cardiac - metabolism
Calcium - metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Catecholamines - pharmacology
Dietary Supplements
Homeostasis - drug effects
Isoproterenol - pharmacology
Male
Mice, Inbred Strains
Myocardial Ischemia - complications
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Nitro Compounds - pharmacology
Oleic Acids - pharmacology
Phosphorylation - drug effects
Ryanodine Receptor Calcium Release Channel - metabolism
Tachycardia, Ventricular - etiology
Tachycardia, Ventricular - prevention & control
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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, NO -OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO -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 Ca leak. NO -OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO -OA might be a novel pharmacological option for the prevention of VT development.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-71870-6