Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation

0456654 - BFÚ 2016 RIV NL eng J - Článek v odborném periodiku
Rudolph, T.K. - Ravekes, T. - Klinke, A. - Friedrichs, K. - Mollenhauer, M. - Pekarová, Michaela - Ambrožová, Gabriela - Martíšková, Hana - Kaur, J.J. - Matthes, B. - Schwoerer, A. - Woodcock, S.R. - Kubala, Lukáš - Freeman, B.A. - Baldus, S. - Rudolph, V.
Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation.
Cardiovascular Research. Roč. 109, č. 1 (2016), s. 174-184. ISSN 0008-6363. E-ISSN 1755-3245
Grant CEP: GA ČR(CZ) GP13-40824P; GA MŠMT(CZ) EE2.3.30.0030
Grant ostatní: GAAV(CZ) M200041208
Institucionální podpora: RVO:68081707
Klíčová slova: Atrial fibrillation * Fibrosis * Nitro-fatty acids
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 5.878, rok: 2016

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.
Trvalý link: http://hdl.handle.net/11104/0257151