Abstract 11439: A Role of Esophageal Cancer Related Gene-4 for Atrial Fibrillation
Introduction: Epidemiological studies have shown that the incidence of atrial fibrillation(AF), the most common type of arrthymia, is more than doubled in cancer patients than that in general population, and reciprocally that the incidence of tumor is ten times higher in AF patients than in non-AF patients. However, the molecular link between tumor and AF remain obscure. Esophageal Cancer Related Gene-4 (Ecrg4), a newly-discovered tumor suppressor gene that is highly expressed in atria and conduction systems of heart, has been shown to function as a ‘sentinel’ molecule in tissue homeostasis, meaning that the presence of Ecrg4 calls for no actions, whereas the loss of Ecrg4 upon injury causes the activation of pro-inflammatory cascade and proliferative responses including fibrosis.
Hypothesis: Since injury-induced loss of Ecrg4 in tumor leads to systemic inflammation and increased fibrosis that are well-known inducing factors to AF, we hypothesize that Ecrg4 in heart plays a critical role in the pathogenesis of AF.
Methods: The expression of Ecrg4 was evaluated by IHC, IF, and RT-PCR. Canine AF model was established by rapid right atrial pacing at 600 beats/min. for 6 hours.
Results: The expression of Ecrg4 was higher in atria and conduction systems than that in ventricles of rat heart by IHC, which was confirmed by RT-PCR. In neonatal rat cardiomyocytes, the expression of Ecrg4, localized in perinucler region and in the ER, is higher in atria than in ventricles. Knock-down Ecrg4 expression by siRNA in atrial cardiomyocytes significantly shortened the duration of action potential. Moreover, in a canine AF model, the expression of Ecrg4 in both Sinus node and left atria was significantly down-regulated compared to that in control animals.
Conclusions: Expression of Ecrg4 is high in atria and heart conduction systems and down-regulated in AF, suggesting that Ecrg4 may play a critical role in the pathogenesis of AF.
Author Disclosures: H. Yu: None. L. Huang: None. X. Fan: None. J. Cheng: None. P. Li: None. X. Fan: None. X. Zeng: None. X. Dang: Research Grant; Modest; Government of Luzhou, 2015LZCYD-S03. Research Grant; Significant; Natural Science Foundation of China,81570277.
- © 2016 by American Heart Association, Inc.