Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis
Martin Mollenhauer, Dennis Mehrkens, Anna Klinke, Max Lange, Lisa Remane, Kai Friedrichs, Simon Braumann, Simon Geißen, Sakine Simsekyilmaz, Felix Sebastian Nettersheim, Samuel Lee, Gabriel Peinkofer, Anne Geisler, Bianca Geis, Alexander Peter Schwoerer, Lucie Carrier, Bruce Α. Freeman, Matthias Dewenter, Xiaojing Luo, Ali El‐Armouche, Michael Wagner, Matti Adam, Stephan Baldus, Volker Rudolph
Abstract
Abstract 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 2 -OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO 2 -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 2+ leak. NO 2 -OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO 2 -OA might be a novel pharmacological option for the prevention of VT development.