Abstract 14577: Nitrated Fatty Acids Suppress Angiotensin II Mediated Atrial Fibrillation in Mice
Background: Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. Nitrated fatty acids (NO2-FA) represent endogenously generated biomolecules which modulate the leukocytes activation state. We have shown recently that atrial fibrillation (AF) is closely linked to leukocyte-derived acceleration of atrial fibrosis. Whether NO2-FA modulate the AF-susceptibility remains unknown.
Methods and Results: Wild-type C57BL6/J mice were treated for 2 weeks with angiotensin II and vehicle or nitro-oleic acid (OA-NO2, 6 mg/kg bodyweight, n=5-8) via subcutanous minipumps. Animals treated with OA-NO2 displayed a strikingly attenuated vulnerability for atrial fibrillation during right atrial electrophysiological stimulation as compared to vehicle-treated animals (total time of atrial fibrillation episodes/animal: 10.026 ± 4.993 vs. 53.838 ± 12.661 sec, p<0.02). Picrosirius red staining revealed that OA-NO2 treatment significantly reduced atrial fibrosis. As a possible underlying molecular mechanism, in vivo studies showed that OA-NO2 markedly inhibited matrix metalloproteinase-9 expression and activity (7.0 vs. 12.1 delta/μ g)- an enzyme involved in matrix degradation and myocardial remodeling. In addition, leukocyte activation was reduced by OA-NO2 (vehicle vs. OA-NO2 (250 nM) treated macrophages (i) superoxide production: 1.46 ± 0.13 vs. 0.67 ± 0.09 mM/h, p=0.02; (ii) oxidative burst 320 ± 30 vs. 270 ± 21 CL (RLU*1000), p=0.04).
Conclusions: These current findings not only revisit the significance of leukocyte activation and structural remodelling for the pathophysiology of atrial fibrillation, but reveal that nitrated fatty acids - by suppressing the inducibility of AF - exhibit potent antiarrhythmic properties.
- © 2012 by American Heart Association, Inc.