Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation

Objectives: The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). Background: AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Methods: Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-alpha 5, and transforming growth factor-beta 1 (TGF-beta 1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-alpha 5. Results: Calreticulin, integrin-alpha 5, and TGF-beta 1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-alpha 5. Integrin-alpha 5 expression correlated with TGF-beta 1 expression, while calreticulin expression correlated with integrin-alpha 5 and TGF-beta 1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Conclusions: Calreticulin, integrin-alpha 5, and TGF-beta 1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.