Abstract 15420: Short-Term Rapid Atrial Pacing Augmented Gene Expression of Proinflammatory Molecules in the Rat Liver
Background: Recent evidences imply close relationship between atrial fibrillation (AF) and inflammation. However, it is still controversial whether inflammation is a cause or a consequence of AF. The liver is a major source of a diverse array of inflammation-related molecules.
Purpose: The aim of this study was to clarify whether the rapid atrial excitation per se promotes systemic inflammation by investigating gene expression profiles of the liver in human AF and rat model.
Methods and Results: We retrospectively screened 465 patients with non-alcoholic steatohepatitis, who underwent liver biopsy from 2003 to 2013, and identified patients with AF. Patients in sinus rhythm matched for age, sex, hepatic histopathological stage, served as a control group. Using cDNA microarray, we compared gene expression profiles of the liver in 2 groups. Hierarchical clustering with 54675 genes showed clear clusters in 2 groups, suggesting the cardio-hepatic interactions in AF. To assess whether rapid atrial excitation per se affects hepatic gene expression profile, we subjected healthy Sprague-Dawley rats to 12-hour rapid atrial pacing at 1200 bpm and analyzed their livers. The 20518 genes demonstrated clear clusters for the pacing or sham group. As with human AF, rapid atrial pacing in rat significantly altered the hepatic gene expression profiles associated with NF-κB pathway (Figure) and acute inflammation pathway. Notably, the heaptic expressions of proinflammatory molecules, including interleukin 1 receptor type 1, TNFRSF1A associated via death domain and conserved helix-loop-helix ubiquitous kinase, were augmented in the rat model, but not in human AF.
Conclusions: The short-term rapid atrial excitation augmented the expressions of proinflammatory molecules remotely in the liver. The present results suggest that acute AF per se can promote systemic inflammation.
Author Disclosures: N. Kanamori: None. T. Kato: None. T. Yaegashi: None. S. Usui: None. H. Furusho: None. S. Takashima: None. H. Murai: None. S. Kaneko: None. M. Takamura: None.
- © 2016 by American Heart Association, Inc.