REV-ERBa Ameliorates Heart Failure Through Transcription Repression

Heart failure remains a major unmet clinical need and current therapies targeting neurohomonal and hemodynamic regulation have limited efficacy. We report that pharmacological activation of the transcriptional repressor REV-ERBa prevents expression of a pathological gene program and cardiomyocyte hypertrophy. In vivo, REV-ERBa agonism prevents development and halts progression of heart failure in mouse models. Thus, modulation of gene networks by targeting REV-ERBa represents a novel approach to heart failure therapy. Overall design: We performed RNAseq on NRVM at baseline and after PE stimulation (4 hr and 48 hr) in the presence or absence of SR9009 (SR or Veh were given 24 hr prior to PE).

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Zhang L, Zhang R, Tien CL, Chan RE, Sugi K, Fu C, Griffin AC, Shen Y, Burris TP, Liao X, Jain MK