标题：Targeting histone deacetylases: perspectives for epigenetic-based therapy in cardio-cerebrovascular disease
作者：Wang, Zi-Ying; Qin, Wen; Yi, Fan
作者机构：[Wang, Z.-Y] Department of Pharmacology, Shandong University, School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong, 250012, China;[ Qin, W] Dep 更多
通讯作者地址：[Yi, F]Shandong Univ, Sch Med, Dept Pharmacol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
关键词：Histone deacetylase;Epigenetic modification;Heart failure;Atherosclerosis;Stroke
摘要：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.