Targeting histone deacetylases: perspectives for epigenetic-based therapy in cardio-cerebrovascular disease.
Targeting histone deacetylases: perspectives for epigenetic-based therapy in cardio-cerebrovascular disease.
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DOI：
10.11909/j.issn.1671-5411.2015.02.010
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Yi F
中科院分区：
文献类型：
--
作者：
Wang ZY;Qin W;Yi F
虽然心脑血管疾病（CCVD）的发病机制是多因素的，但越来越多的实验和临床研究强调了组蛋白去乙酰化酶（HDAC）介导的表观遗传过程在心脑血管损伤发展中的重要性。HDAC是一个酶家族，用于平衡组蛋白乙酰转移酶对染色质重塑的乙酰化活性，并在调节基因转录方面发挥重要作用。到目前为止，18哺乳动物HDAC被确定，并根据与酵母直系同源物的相似性分为四类。锌依赖性HDAC家族目前由11个成员组成，根据结构、序列同源性和结构域组织分为三类（I类、II类和IV类）。相比之下，III类HDAC（也称为sirtuins）由与Sir2基因相关的NAD+依赖性蛋白质修饰酶家族组成。HDAC抑制剂是一组通常通过结合HDAC的含锌催化结构域来阻断HDAC活性的化合物，并且在心脑血管系统中显示出抗炎和抗纤维化作用。本文就HDACs的分类、功能及其在心脑血管系统中的作用和调控机制作一综述。HDAC介导的表观遗传过程的药理学靶向可能为治疗CCVD开辟新的治疗途径。
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 anti-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 targeting of HDAC-mediated epigenetic processes may open new therapeutic avenues for the treatment of CCVD.
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影响因子：
64.5
作者：
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通讯作者：
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DOI：
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发表时间：
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作者：
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