Transcriptome Discovery of Genes in the Three Phases of Autophagy That Are Upregulated During Atrial Fibrillation.

Abstract

Background: Autophagy may contribute to the maintenance of atrial fibrillation (AF), but no previous study has concurrently surveyed all 3 phases of autophagy, namely autophagosome formation, lysosome formation, and autophagosome-lysosome fusion. Here we aimed to identify disorders involving various phases of autophagy during AF. Methods and Results: We used bioinformatic techniques to analyze publicly available DNA microarray datasets from the left atrium (LA) and right atrium (RA) of 7 patients with AF and 6 patients with normal sinus rhythm who underwent valvular surgeries. We compared gene expression levels in the LA (AF-LA) and RA of patients with AF with those in the LA and RA of patients with normal sinus rhythm. Several differentially expressed genes in the AF-LA sample were significantly associated with the Gene Ontogeny term 'Autophagy', indicating that the expression of autophagic genes was specifically altered in this dataset. In particular, the expression of genes known or suspected to be involved in autophagosome formation (autophagy related 5 [ATG5], autophagy related 10 [ATG10], autophagy related 12 [ATG12], and light chain 3B [LC3B]), lysosome formation (lysosomal associated membrane protein 1 [LAMP1] and lysosomal associated membrane protein 2 [LAMP2]), and autophagosome-lysosome fusion (synaptosome associated protein 29 [SNAP29], SNAP associated protein [SNAPIN], and syntaxin 17 [STX17]) was significantly upregulated in the LA-AF dataset. Conclusions: Autophagy is activated excessively in, and may perpetuate, AF.