Mollenhauer, Martin, Mehrkens, Dennis ORCID: 0000-0002-8578-0290, 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 and Rudolph, Volker (2020). Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis. Sci Rep, 10 (1). BERLIN: NATURE RESEARCH. ISSN 2045-2322

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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, 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mollenhauer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehrkens, DennisUNSPECIFIEDorcid.org/0000-0002-8578-0290UNSPECIFIED
Klinke, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lange, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Remane, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedrichs, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braumann, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geissen, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simsekyilmaz, SakineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nettersheim, Felix S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, SamuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peinkofer, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geisler, Anne C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geis, BiancaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwoerer, Alexander P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carrier, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freeman, Bruce A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dewenter, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luo, XiaojingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Armouche, AliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adam, MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldus, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudolph, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-318871
DOI: 10.1038/s41598-020-71870-6
Journal or Publication Title: Sci Rep
Volume: 10
Number: 1
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACUTE MYOCARDIAL-INFARCTION; SR CA2+ LEAK; OXIDE; PHOSPHORYLATION; EXPRESSION; OUTCOMES; CURRENTS; MODELMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31887

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