ETV1 activates a rapid conduction transcriptional program in rodent and human cardiomyocytes
Year: 2018
Type: article
Abstract: Rapid impulse propagation is a defining attribute of the pectinated atrial myocardium and His-Purkinje system (HPS) that safeguards against atrial and ventricular arrhythmias, conduction block, and myocardial dyssynchrony. The complex transcriptional circuitry that dictates rapid conduction remains incompletely understood. Here, we demonstrate that ETV1 (ER81)-dependent gene networks dictate the unique electrophysiological characteristics of atrial and His-Purkinje myocytes. Cardiomyocyte-specific deletion of ETV1 results in cardiac conduction abnormalities, decreased expression of rapid conduction genes (Nkx2-5, Gja5, and Scn5a), HPS hypoplasia, and ventricularization of the unique sodium channel properties that define Purkinje and atrial myocytes in the adult heart. Forced expression of ETV1 in postnatal ventricular myocytes (VMs) reveals that ETV1 promotes a HPS gene signature while diminishing ventricular and nodal gene networks. Remarkably, ETV1 induction in human induced pluripotent stem cell-derived cardiomyocytes increases rapid conduction gene expression and inward sodium currents, converting them towards a HPS phenotype. Our data identify a cardiomyocyte-autonomous, ETV1-dependent pathway that is responsible for specification of rapid conduction zones in the heart and demonstrate that ETV1 is sufficient to promote a HPS transcriptional and functional program upon VMs.
Source: Scientific Reports
Institutions: NYU Langone Health, New York University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: U.S. Department of Health and Human Services, American Heart Association, Memorial Sloan-Kettering Cancer Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
Awards: ETV1-Dependent Regulation of the Fast Cardiac Conduction Phenotype, Etv1 is an Essential Regulator of Fast Conduction Tissues in the Heart, G3632629470, Institutional Clinical and Translational Science Award, G5209949983, G5318323681, Purkinje Cells and Arrhythmia Mechanisms, Training in Pharmacological Sciences, NRG-1 dependent transcriptional networks that dictate Purkinje cell fate decisions, Clinical and Translational Science Award
OpenAlex ID: W2810439806