Food Bioactive HDAC Inhibitors in the Epigenetic Regulation of Heart Failure.
Food Bioactive HDAC Inhibitors in the Epigenetic Regulation of Heart Failure.
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DOI：
10.3390/nu10081120
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发表时间：
2018-08-18
期刊：
影响因子：
5.9
通讯作者：
Ferguson BS
中科院分区：
文献类型：
--
作者：
Evans LW;Ferguson BS
大约570万美国成年人被诊断患有心力衰竭（HF）。更令人担忧的是，美国每9例死亡中就有1例心衰是导致死亡的原因。目前的HF药物（如β受体阻滞剂，ACEi）靶向细胞表面受体下游的细胞内信号级联，以防止心脏泵功能障碍。然而，这些药物不能靶向其他冗余的细胞内信号通路，因此限制了药物疗效。因此，人们假设设计针对这些信号通路共享的下游介质的化合物对HF的治疗更有效。组蛋白去乙酰化已被认为是心衰发展的关键致病因素。赖氨酸残基经历了多种可逆的翻译后修饰，包括乙酰化，历史上作为染色质内组蛋白尾部的表观遗传修饰剂被研究，为调节基因表达提供了重要的机制。最近，我们饮食中的生物活性化合物与基因表达的调节有关，部分是通过调节外显基因组。据报道，食品生物活性物质通过直接调节writer（组蛋白乙酰转移酶，hat）和eraser（组蛋白去乙酰化酶，hdac）蛋白来调节组蛋白乙酰化。因此，生物活性食物化合物作为心力衰竭的表观遗传修饰剂提供了独特的治疗策略。本文将重点介绍食品生物活性作为心脏组蛋白去乙酰化酶活性的调节剂。
Approximately 5.7 million U.S. adults have been diagnosed with heart failure (HF). More concerning is that one in nine U.S. deaths included HF as a contributing cause. Current HF drugs (e.g., β-blockers, ACEi) target intracellular signaling cascades downstream of cell surface receptors to prevent cardiac pump dysfunction. However, these drugs fail to target other redundant intracellular signaling pathways and, therefore, limit drug efficacy. As such, it has been postulated that compounds designed to target shared downstream mediators of these signaling pathways would be more efficacious for the treatment of HF. Histone deacetylation has been linked as a key pathogenetic element for the development of HF. Lysine residues undergo diverse and reversible post-translational modifications that include acetylation and have historically been studied as epigenetic modifiers of histone tails within chromatin that provide an important mechanism for regulating gene expression. Of recent, bioactive compounds within our diet have been linked to the regulation of gene expression, in part, through regulation of the epi-genome. It has been reported that food bioactives regulate histone acetylation via direct regulation of writer (histone acetyl transferases, HATs) and eraser (histone deacetylases, HDACs) proteins. Therefore, bioactive food compounds offer unique therapeutic strategies as epigenetic modifiers of heart failure. This review will highlight food bio-actives as modifiers of histone deacetylase activity in the heart.
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