Role of the Calpain System in Pulmonary Vein Connexin Remodeling in Dogs with Atrial Fibrillation

Abstract

Objectives: Changes in connexins and calpains of the myocardial sleeve of the pulmonary vein and the left atrium were investigated in chronic atrial fibrillation (AF) animal models. Background: There are no reports of changes in the calpain system and connexins in the pulmonary vein where AF is initiated. Methods: An AF animal model was prepared by rapid pacing of the right atrium for 8 weeks. Histological changes of pulmonary veins were analyzed by Masson trichrome staining, and mRNA as well as protein expression of connexins and calpains were measured by real-time fluorescence quantitative PCR and Western blotting. Results: In AF dogs, the fibrous collagen reticulum surrounding individual myocardial cells was reduced or disrupted. In the myocardial sleeve of the AF dogs, Cx40 protein expression was significantly downregulated compared to the control group (60.78 ± 10.91 vs. 88.31 ± 14.73, p < 0.05), but calpain 1 was significantly upregulated (94.00 ± 7.24 vs. 81.77 ± 5.82, p < 0.05), and they were negatively correlated (r = –0.66, p < 0.05). Cx40 protein expression was significantly lower in the myocardial sleeve tissue than in the left atrium in the AF dogs (60.78 ± 10.91 vs. 91.38 ± 17.16, p < 0.05). Conclusions: Varied gap junctional remodeling around the pulmonary vein may be one of the underlying mechanisms for pulmonary vein-left atrial reentry. During AF, the calpain system of the myocardial sleeve tissue is activated and may hydrolyze Cx40 protein, which is a possible important molecular mechanism for gap junctional remodeling that merits further investigation.