2016 AHA Late-Breaking Basic Science Abstracts.

Abstract

### 23633 ### The Transcription Factor Early B-cell Factor 1 is Critical for Proper Formation of the Cardiac Ventricular Conduction System Eugene Kim, Akshay Shekhar, Jie Zhang, Fang-Yu Liu, Wilson Young, Glenn I Fishman; New York Univ Sch of Medicine, New York, NY Transcriptional regulation of cardiac ventricular conduction system (VCS) development is incompletely understood. Using gene expression profiling of the VCS using the Cntn2-EGFP transgenic VCS fluorescent reporter mouse, we identified Early B-cell Factor 1, Ebf1 , as being significantly enriched in the VCS. Surface electrocardiography of the Ebf1 knockout mouse revealed ventricular conduction slowing as evidences by QRS widening; echocardiography using strain imaging revealed marked left ventricular dyssynchrony; and wholemount imaging of the Ebf1 KO heart demonstrated dramatic hypoplasia of the VCS. Gene expression profiling was performed on E13.5 embryonic hearts using deep sequencing and a number of transcription factors known to be critical for cardiogenesis were markedly reduced, including Nkx 2–5, Gata4, Hand1, Irx3 , and Irx5 . Histological analysis of embryonic hearts revealed marked cellular hyperplasia and staining for markers of cell cycle (Ki-69; phospho-histone H3) were consistent with exuberant cellular proliferation. Quantitative immunofluorescence for several markers of terminally differentiated VCS cells was performed and demonstrated reduced expression of Nkx 2–5, Scn5a , and Cx40 , particularly within the terminal Purkinje fibers of the VCS. Finally, analysis of the Nkx 2–5 promoter revealed a highly conserved Ebf1 binding site in a region previously described as critical for proper expression of Nkx 2–5 in the VCS. Using CRISPR-Cas9 mediated gene editing, a 200 bp region flanking this site was deleted and the mutant mice generated also demonstrated marked QRS widening, phenocopying the Ebf1 KO. Author Disclosures: E. Kim: None. A. Shekhar: None. J. Zhang: None. F. Liu: None. W. Young: None. G.I. Fishman: None. Key Words: Cardiac development; Biology, developmental; Cardiovascular development; Electrophysiology; Heart conduction system ### 23347 ### Intramyocardial Delivery of miR-199a Reduces Scar Size and Preserves Contractile Function In Infarcted Pig Hearts Khatia Gabisonia; Sant’Anna Sch of Advanced Studies, Pisa, Italy We have previously …