Michael T Broman, Rangarajan D Nadadur, Carlos Perez-Cervantes, Ozanna Burnicka-Turek, Sonja Lazarevic, Anna Gams, Brigitte Laforest, Jeffrey D Steimle, Sabrina Iddir, Zhezhen Wang, Linsin Smith, Stefan R Mazurek, Harold E Olivey, Pingzhu Zhou, Margaret Gadek, Kaitlyn M Shen, Zoheb Khan, Joshua W M Theisen, Xinan H Yang, Kohta Ikegami, Igor R Efimov, William T Pu, Christopher R Weber, Elizabeth M McNally, Eric C Svensson, Ivan P Moskowitz
BACKGROUND: The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by ZFPM2 ) is observed in human ventricles during HF and causes HF in mice. METHODS: FOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription...
January 8, 2024: Circulation