Berry Jeff M, Cao Dian J, Rothermel Beverly A, Hill Joseph A
University of Texas Southwestern Medical Center, Donald W Reynolds Cardiovascular Clinical Research Center, Dallas, Texas, USA.
Expert Opin Drug Saf. 2008 Jan;7(1):53-67. doi: 10.1517/14740338.7.1.53.
Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. Studies in preclinical models suggest that inhibition of histone deacetylase (HDAC) activity - using compounds that show promise in ongoing oncology trials - blunts pathologic growth of cardiac myocytes. Indeed, small-molecule inhibitors of HDACs are members of an evolving class of pharmacologic agents in development for the treatment of several diseases. If proved effective in the treatment of heart disease, HDAC inhibitors could have a significant impact on public health, as cardiovascular disease remains the leading cause of death in the US. This paper reviews understanding of the mechanisms of action of HDAC inhibitors in the heart and summarizes emerging data regarding their effects on disease-related cardiac remodeling and function.
近期研究表明，染色质重塑，尤其是组蛋白乙酰化，在心脏基因表达调控中具有重要作用。临床前模型研究表明，使用在当前肿瘤学试验中显示出前景的化合物抑制组蛋白脱乙酰酶（HDAC）活性，可抑制心肌细胞的病理性生长。事实上，HDAC的小分子抑制剂是正在开发用于治疗多种疾病的一类不断发展的药物。如果HDAC抑制剂在心脏病治疗中被证明有效，那么鉴于心血管疾病仍是美国的主要死因，它可能会对公众健康产生重大影响。本文综述了对HDAC抑制剂在心脏中的作用机制的理解，并总结了有关其对疾病相关心脏重塑和功能影响的新数据。
