Abstract 1080: Expression of RAGE in Diabetic Rat Atria - Mechanisms of Diabetes-related Atrial Structural Remodeling
Background - Many epidemiological studies have demonstrated that diabetes mellitus (DM) is commonly associated with the development of atrial fibrillation (AF). Nonetheless, the precise pathophysiological relationships between AF and DM are not well understood. We sought to test the hypothesis that DM promotes structural changes of atria in connection with the advanced glycation end products (AGE) and the receptor for AGE (RAGE), which have been recently implicated in the pathogenesis of diabetic complications.
Methods and Results - DM was induced by streptozotocin at 65 mg/kg i.p. in 8-week-old female Sprague-Dawley rats. Diabetic animals were randomized into two groups, which were fed either normal or 0.28% OPB-9195 (a inhibitor of advanced glycation) mixed rat chow. At 24 weeks old, their hearts were subjected for histological and immunohistochemical studies. The HbA1c value of induced-DM rats was significantly higher than that of control rats and did not significantly improve by OPB-9195. Histological and immunohistochemical examinations revealed that the atria of diabetic rats showed remarkable structural changes characterized by diffuse interstitial fibrosis and that they presented with abundant expressions of RAGE. Treatment with OPB-9195 effectively suppressed this diabetes-induced atrial fibrosis in conjunction with reduced expression of RAGE.
Conclusion - The present study indicated for the first time that DM promoted structural remodeling in rat atria and that AGE-RAGE system played an important role in the pathogenesis. This provides a potential new upstream therapeutic approach for diabetes-related atrial tachyarrhythmias.