HDAC inhibition as a therapeutic strategy in myocardial ischemia/reperfusion injury.
HDAC inhibition as a therapeutic strategy in myocardial ischemia/reperfusion injury.
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DOI：
10.1016/j.yjmcc.2019.02.013
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发表时间：
2019-02
影响因子：
5
通讯作者：
Min Xie;Yida Tang;Joseph A. Hill
中科院分区：
文献类型：
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作者：
Min Xie;Yida Tang;Joseph A. Hill
心肌梗死期间的再灌注损伤约占最终梗死面积的一半。尽管这已经知道了几十年，但靶向再灌注损伤的有效治疗仍然难以捉摸。许多蛋白质会发生可逆的乙酰化，肿瘤学中已经出现了靶向控制这些事件的酶的药物。其中，靶向蛋白质脱乙酰酶的小分子，即所谓的组蛋白脱乙酰酶（HDAC），已被批准用于罕见癌症的人类用途。现在，来自多个实验室以及小鼠和大型动物的工作已经证明，使用批准用于临床使用的化合物的HDAC抑制在心肌再灌注时提供强大的心脏保护。在这里，我们总结了这门科学的关键基础，讨论了潜在的机制，并为首次人体临床试验提供了一个框架。
Reperfusion injury during myocardial infarction accounts for approximately half of final infarct size. Whereas this has been known for decades, efficacious therapy targeting reperfusion injury remains elusive. Many proteins are subject to reversible acetylation, and drugs targeting enzymes that govern these events have emerged in oncology. Among these, small molecules targeting protein deacetylating enzymes, so-called histone deacetylases (HDACs), are approved for human use in rare cancers. Now, work emerging from multiple laboratories, and in both mice and large animals, has documented that HDAC inhibition using compounds approved for clinical use confers robust cardioprotection when delivered at the time of myocardial reperfusion. Here, we summarize the key underpinnings of this science, discuss potential mechanisms, and provide a framework for a first-in-human clinical trial.