组蛋白去乙酰化酶在调节心肌肥大过程中的作用机制

The mechanism underlying histone deacetylases regulating cardiac hypertrophy

心肌肥大(cardiac hypertrophy)是由外周组织对血流动力学需求增加而发生的一种代偿性反应。在心肌肥大过程中,不同时期的不同类型的基因表达受到生理和病理信号的多级转录调控。组蛋白乙酰化作为最广泛的翻译后修饰方式,受相互拮抗的组蛋白乙酰化酶(histone acetyltransferases,HAT)和组蛋白去乙酰化酶(histone deacetylases,HDACs)的精细控制。近年来研究表明,HDACs作为一类抑制转录过程并含有高度保守的脱乙酰酶结构域家族酶,通过多种作用途径调控心肌肥大过程中的基因表达。本文主要综述了组蛋白去乙酰化酶调节心肌肥大过程的相关研究进展,通过阐明不同种类HDACs在心肌肥大中的作用和分子机制,为不同类型心肌肥大和心衰的发病治疗提供新的思路,为新药设计提供分子靶点。

Cardiac hypertrophy is a compensatory response that occurs as a result of increased hemodynamic requirement in peripheral tissues.In the process of cardiac hypertrophy,the expression of different types of genes in different stages is transcriptionally regulated by multiple-level physiological and pathological signals.Histone acetylation,as the most extensive post-translational modification,is closely controlled by the antagonistic histone acetyltransferases(HAT)and histone deacetylases(HDACs).Recent studies have shown that HDACs,as a family of enzymes that inhibit transcription and contain highly conserved deacetylase domains,regulate gene expression during cardiac hypertrophy through a variety of pathways.In this review,we mainly summarize the research progress on histone deacetylase in cardiac hypertrophy.By elucidating the role and molecular mechanism of different HDACs in cardiac hypertrophy,it provides new ideas for the treatment of different types of cardiac hypertrophy and heart failure,and molecular targets for new drug design.