REV-ERBα 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.心力衰竭仍是一项亟待满足的重大临床需求，当前针对神经激素（neurohormonal）与血流动力学调控的治疗方案疗效有限。本研究证实，转录抑制因子REV-ERBα（transcriptional repressor REV-ERBα）的药理学激活可阻断病理性基因程序的表达与心肌细胞肥大。在活体小鼠模型中，REV-ERBα激动剂可阻止心力衰竭的发生并阻断其进展。因此，以REV-ERBα为靶点调控基因网络，可为心力衰竭治疗提供全新策略。