Abstract
Background: The synthesis of the extracellular matrix (ECM) protein, i.e., matricellular proteins, is considered to be related with cardiac fibrosis and remodeling in various cardiovascular diseases. In this study, we analyzed the global responses in mRNA expressions in both atria and ventricles to evaluate the genes which are associated with cardiac fibrosis and remodeling in the canine atrial fibrillation (AF) model. Methods: 14 dogs with implanted pacing devices were divided into pacing (with 6-week pacing, n=7) and sham (without pacing, n=7) groups. The global mRNA expressions were profiled by GeneChip microarray in each group. Results: The 25 genes of the right atrium and 15 genes of the left atrium exhibited significant up-regulations in comparison with sham group. In contrast, both ventricles exhibited only 2 up-regulated genes. The majority of up-regulated genes in atria were matricellular proteins which are predominantly associated with the development of ECM composition, but these up-regulations were not observed in the ventricles. The real-time RT-PCR and western blot analysis exhibited similar results as the microarray analysis. Conclusions: Up-regulations of genes related to ECM synthesis were observed only in the atria but not in the ventricle. This result may indicate a key role of ECM synthesis as the mechanism of myocardial remodeling in AF.
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