Targeting histone deacetylases： perspectives for epigenetic-based therapy in cardio-cerebrovascular disease

尽管致病 of ； cardio 脑血管的疾病(CCVD ) ；是 multifactorial，越来越多的试验性、临床的研究强调了调停的 epigenetic 在 cardio 脑血管的损害的发展处理的 histone deacetylase (HDAC ) 的重要性。HDAC 是酶的一个家庭在染色质在调整基因抄写改变和戏必需品角色上平衡 histone acetyltransferases 的 acetylation 活动。迄今为止， 18 哺乳动物的 HDAC 基于类似被鉴别并且组织班进四到酵母 orthologs。锌依赖者 HDAC 家庭当前由根据结构，顺序相同，和域组织划分成三个类(一级， II，和 IV ) 的 11 个成员组成。在比较，班 III HDAC (也作为 sirtuins 知道) 由 NAD +-dependent 的一个家庭组成与 Sir2 基因有关的修改蛋白质的酶。HDAC 禁止者是由绑定典型地堵住 HDAC 活动到 HDAC 的包含锌的催化的域的一组混合物并且显示了反煽动性并且在 cardio 脑血管的系统的 antifibrotic 效果。在这评论，我们在 cardio 脑血管的系统关于分类， HDAC 的功能和他们的角色和规章的机制总结当前的知识。调停 HDAC 的 epigenetic 过程指向的药理学可以为 CCVD 的处理打开新治疗学的大街。

Although the pathogenesis of cardio-cerebrovascular disease （CCVD） is multifactorial, an increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase （HDAC）-mediated epigenetic processes in the development of cardio-cerebrovascular injury. HDACs are a family of enzymes to balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. To date, 18 mammalian HDACs are identified and grouped into four classes based on similarity to yeast orthologs. The zinc-dependent HDAC family currently consists of 11 members divided into three classes （class I, II, and IV） on the basis of structure, sequence homology, and domain organization. In comparison, class III HDACs （also known as the sirtuins） are composed of a family of NAD＋-dependent protein-modifying enzymes related to the Sir2 gene. HDAC inhibitors are a group of compounds that block HDAC activities typically by binding to the zinc-containing catalytic domain of HDACs and have displayed an- ti-inflammatory and antifibrotic effects in the cardio-cerebrovascular system. In this review, we summarize the current knowledge about classifications, functions of HDACs and their roles and regulatory mechanisms in the cardio-cerebrovascular system. Pharmacological tar- geting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD.