Abstract 8667: Carvedilol Suppresses the Structural Remodeling in the Canine Atrial Fibrillation Model via the Suppression of Periostin as a Mediator of the Extracellular Matrix Synthesis

Abstract

Background: Periostin is a novel extracellular matrix (ECM) protein, secreted from cardiac fibroblasts, and is considered to be related with cardiac fibrosis and remodeling as one of the mediators of ECM synthesis. In our canine atrial fibrillation (AF) model, we have documented that the ECM synthesis was observed as the atrial structural remodeling and the AF inducibility was suppressed by carvedilol, a beta-blocker with the anti oxidative action. In this study, we evaluate the effect of carvedilol against the periostin synthesis and the development of structural remodeling in the canine AF model. Methods: AF model was produced by performing rapid atrial stimulation in 15 dogs. They were divided into 3 groups; 1) carvedilol group (n=5): 6-week pacing with carvedilol (50mg/day), 2) control group (n=5): pacing without carvedilol, and 3) non-pacing group (n=5). At the end of the protocol, atrial tissues were sampled for the evaluation of mRNA and protein expressions of periostin by the real time RT-PCR and the western blot analysis. The immuno-fluorescent staining analysis of periostin and the 8-OHdG, one of the major forms of DNA damage induced by the reactive oxygen species, were performed to evaluate the expression of periostin and oxidative stress in the atrial tissue. Results: The mRNA and protein expressions of periostin were up-regulated in the control in comparison with non-pacing group, and this up-regulation was suppressed by carvedilol (p<0.05). Immuno-fluorescent staining analysis exhibited abundant accumulation of periostin within the interstitial space with the fibrosis in the control, and it was suppressed by carvedilol. In the 8-OHdG staining, enhanced oxidative stress was observed in the atrial tissue in the control, but not in the carvedilol group. Conclusion: Periostin was remarkably up-regulated within the interstitial space in the atria with the fibrosis in our canine AF model. Because this up-regulation was suppressed by carvedilol, periostin up-regulation was speculated to be mediated by the oxidative stress in the AF model.