Region-specific gene expression profiles in the left atria of patients with valvular atrial fibrillation

Background: Previous studies have demonstrated that atrial regions contribute differently to atrial fibrillation (AF) substrate. Pulmonary vein and the surrounding left atrial junction (LA-PV junction) are crucial areas in AF substrates and important ablation targets. Objective: To identify regional differences in the left atria of patients with AF by using a genome-wide approach. Methods: Paired LA-PV junction and left atrial appendage (LAA) specimens were obtained from 16 patients with persistent AF and 3 with sinus rhythm who underwent valvular surgery. The paired specimens were sent for microarray comparison. Results: Of 54,675 expressed sequence tags, microarray analysis in patients with AF revealed that 391 genes were differentially expressed between the LA-PV junction and the LAA, including genes related to arrhythmia, cell death, fibrosis, hypertrophy, and inflammation. Microarray and real time-polymerase chain reaction produced parallel results in analyzing the expression of particular genes. In both patients with AF and sinus rhythm, the LA-PV junction exhibited greater paired-like homeodomain-2 and its target protein (short stature homeobox-2) expression than the LAA, which might contribute to arrhythmogenesis. Five genes related to thrombogenesis were upregulated in the LAA of patients with AF, which might implicate for the preferential thrombus formation in the LAA. Genes related to fibrosis were highly expressed in the LAA of patients with AF, which was reflected by intense ultrastructural changes in this region. Conclusions: We used a genome-wide approach to investigate region-specific gene expression in the left atria. Our findings provide important information relevant to region-specific arrhythmogenesis and thrombogenesis in AF pathogenesis.