Abstract
Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood. This study aimed to identify the functionally enriched gene-sets in AF and capture their interconnection via pivotal factors, that may drive or be driven by AF. Global abundance of the proteins in the left atrium of AF patients compared to control patients (n = 3/group), and the functionally enriched biological processes in AF were determined by mass-spectrometry and gene set enrichment analysis, respectively. The data were validated in an independent cohort (n = 19–20/group). In AF, the gene-sets of innate immune system, metabolic process, cellular component disassembly and ion homeostasis were up-regulated, while the gene-set of ciliogenesis was down-regulated. The innate immune system was over-represented by neutrophil degranulation, the components of which were extensively shared by other gene-sets altered in AF. In the independent cohort, an activated form of neutrophils was more present in the left atrium of AF patients with the increased gene expression of neutrophil granules. MYH10, required for ciliogenesis, was decreased in the atrial fibroblasts of AF patients. We report the increased neutrophil degranulation appears to play a pivotal role, and affects multiple biological processes altered in AF.
Highlights
Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood
Our data suggest that in the left atrial tissue of persistent AF patients neutrophil degranulation is a prominent biological event, the components of which may play a pivotal role interconnecting the other biological processes altered in patients with AF
Many genes of response to bacterium were found to be significantly increased with a higher fold-change in the left atrial tissue of AF patients compared to non-AF patients
Summary
Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood. Global abundance of the proteins in the left atrium of AF patients compared to control patients (n = 3/group), and the functionally enriched biological processes in AF were determined by mass-spectrometry and gene set enrichment analysis, respectively. An activated form of neutrophils was more present in the left atrium of AF patients with the increased gene expression of neutrophil granules. We report the increased neutrophil degranulation appears to play a pivotal role, and affects multiple biological processes altered in AF. Explorative proteomics analysis by high-throughput liquid-chromatography online coupled to tandem mass spectrometry (LC–MS/MS) is a strong tool to uncover the changes in global protein abundance along with the altered biological processes in various diseases, and can thereby give insight into disease biology.
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