Rudolph, Tanja K., Ravekes, Thorben, Klinke, Anna, Friedrichs, Kai, Mollenhauer, Martin, Pekarova, Michaela, Ambrozova, Gabriela ORCID: 0000-0002-8172-9746, Martiskova, Hana, Kaur, Jatinder-Jit, Matthes, Bianca, Schwoerer, Alex, Woodcock, Steven R., Kubala, Lukas ORCID: 0000-0002-7729-7338, Freeman, Bruce A., Baldus, Stephan and Rudolph, Volker (2016). Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation. Cardiovasc. Res., 109 (1). S. 174 - 185. OXFORD: OXFORD UNIV PRESS. ISSN 1755-3245

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Abstract

Aim Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be useful as drug candidates. Herein we investigate whether an exemplary nitro-fatty acid can limit atrial fibrosis and AF. Methods and results Wild-type C57BL6/J mice were treated for 2 weeks with angiotensin II (AngII) and vehicle or nitro-oleic acid (10-nitro-octadec-9-enoic acid, OA-NO2, 6 mg/kg body weight) via subcutaneous osmotic minipumps. OA-NO2 significantly inhibited atrial fibrosis and depressed vulnerability for AF during right atrial electrophysiological stimulation to levels observed for AngII-naive animals. Left atrial epicardial mapping studies demonstrated preservation of conduction homogeneity by OA-NO2. The protection from fibrotic remodelling was mediated by suppression of Smad2-dependent myofibroblast transdifferentiation and inhibition of Nox2-dependent atrial superoxide formation. Conclusion OA-NO2 potently inhibits atrial fibrosis and subsequent AF. Nitro-fatty acids and possibly other lipid electrophiles thus emerge as potential therapeutic agents for AF, either by increasing endogenous levels through dietary modulation or by administration as synthetic drugs.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rudolph, Tanja K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ravekes, ThorbenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klinke, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedrichs, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mollenhauer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pekarova, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ambrozova, GabrielaUNSPECIFIEDorcid.org/0000-0002-8172-9746UNSPECIFIED
Martiskova, HanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaur, Jatinder-JitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matthes, BiancaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwoerer, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woodcock, Steven R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubala, LukasUNSPECIFIEDorcid.org/0000-0002-7729-7338UNSPECIFIED
Freeman, Bruce A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldus, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudolph, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-291648
DOI: 10.1093/cvr/cvv254
Journal or Publication Title: Cardiovasc. Res.
Volume: 109
Number: 1
Page Range: S. 174 - 185
Date: 2016
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1755-3245
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OXIDATIVE STRESS; NITRIC-OXIDE; TASK-FORCE; EXPRESSION; SUPEROXIDE; TISSUE; CONNEXIN-43; CONTRIBUTES; ACTIVATION; MECHANISMSMultiple languages
Cardiac & Cardiovascular SystemsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/29164

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