Gene expression differs between the left atrial appendage and the left atrial wall in patients with long-term persistent atrial fibrillation

Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide and a significant contributor to cardiovascular morbidity and mortality. Although some studies have investigated differences in gene expression between the left and right atrial appendages, there are few studies within the same left atrium, and its characteristics are largely unclear. We collected multiple samples from the same left atrium of patients diagnosed with long-standing persistent with AF and analyzed differences in gene expression. Methods Left atrial tissues were taken from the resected left atrial appendage (APP) and the left atrial wall (WAL; right side or ceiling) in nine patients with AF who underwent valve surgery with/without Maze procedure, and were embedded in a formalin-fixed paraffin block until analysis. RNA was extracted using NucleoSpin Total RNA FFPE XS, and the concentration and purity of the sample were measured with NanoPhotometer N50. After RNA quantification, a comprehensive microarray analysis of six specimens (3 each in the APP and WAL groups) was performed by the outsourcer company. Based on the microarray results, the differentially expressed genes were further validated using quantitative reverse transcription-polymerase chain reaction (RT-PCR) in nine patients. Results When we extracted genes whose expression changed by 2-fold or more between the two groups, 1585 genes were identified. Focusing on genes whose expression differed by 30-fold or more, sarcolipin (SLN) was down-regulated in the WAL group. On the other hand, actin alpha1 (ACTA1), myosin light chain 2 (MYL2), and interleukin-6(IL-6) were down-regulated in the APP group. RT-PCR significantly showed elevated ACTA1 (relative quantification (RQ): 4.85) and MYL2 (RQ: 10.5), reduced SLN (RQ: 0.33) in the WAL group as compared to the APP group. Conclusion Even in the left atrium of the same patient, sarcolipin decreased and conversely both of actin and myosin increased in the left atrial wall. The differing expression of genes in both left atrial wall and left atrial appendage may indicate that there are different mechanisms for development, support and remodeling of AF even within the left atrium.