McKinsey Timothy A
Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO 80045-0508, USA.
Handb Exp Pharmacol. 2011;206:57-78. doi: 10.1007/978-3-642-21631-2_4.
The heart responds to stresses such as chronic hypertension and myocardial infarction by undergoing a remodeling process that is associated with myocyte hypertrophy, myocyte death, inflammation and fibrosis, often resulting in impaired cardiac function and heart failure. Recent studies have revealed key roles for histone deacetylases (HDACs) as both positive and negative regulators of pathological cardiac remodeling, and small molecule HDAC inhibitors have demonstrated efficacy in animal models of heart failure. This chapter reviews the functions of individual HDAC isoforms in the heart and highlights issues that need to be addressed to enable development of novel HDAC-directed therapies for cardiovascular indications.
心脏会通过经历一个重塑过程来应对诸如慢性高血压和心肌梗死等应激,该过程与心肌细胞肥大、心肌细胞死亡、炎症和纤维化相关,常导致心脏功能受损和心力衰竭。最近的研究揭示了组蛋白脱乙酰酶(HDACs)作为病理性心脏重塑的正向和负向调节因子的关键作用,并且小分子HDAC抑制剂已在心力衰竭动物模型中显示出疗效。本章综述了各个HDAC亚型在心脏中的功能,并强调了为开发针对心血管适应症的新型HDAC导向疗法而需要解决的问题。