Basic/Translational Science -> Genomics: Bench D-PO03 - Poster Session III (ID 48) Poster

D-PO03-021 - Cardiac Pressure Overload Decreases Etv1 Expression In The Left Atrium, Contributing To Atrial Remodeling And Arrhythmogenesis (ID 275)

Abstract

Background: Elevated intracardiac pressure due to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias The underlying molecular pathways that drive atrial remodeling in cardiac pressure overload states are poorly defined
Objective: We aimed to characterize the response of the ERBB4/ETV1 signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the functional consequences of ETV1 loss in atrial arrhythmogenesis
Methods: Gene profiling was performed on total RNA extracted from left atrial specimens obtained during cardiac surgery at the Cleveland Clinic and pressure overloaded mouse models with trans-aortic constriction (TAC) banding or angiotensin II (Ang II) infusion
Results: ETV1 expression was decreased in patients with lower ejection fraction Consistent with its role as an important mediator of the Neuregulin-1 (NRG1) signaling pathway and activator of rapid conduction gene programming, ETV1 expression was associated with NRG1, ERBB4, SCN5A, and GJA5 levels in human LA samples In the two cardiac-pressure overload murine models, LA Etv1 was downregulated at the transcriptional level Cardiac pressure overload produced a consistent downregulation of Erbb4, Etv1, Scn5a and Gja5 and upregulation profibrotic gene programming, such as Tgfbr1/2 Interestingly, an Etv1 knockout LA RNA-seq dataset recapitulated the reduction in rapid conduction genes and upregulation of profibrotic gene programming
Conclusion: ETV1 is downregulated in the LA during cardiac pressure overload in humans and mice, contributing to both electrical and structural remodeling
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