College of Literature Science and the Arts University of Michigan Ann Arbor MI.
Department of Emergency Medicine Michigan Medicine University of Michigan Ann Arbor MI.
J Am Heart Assoc. 2020 Jun 2;9(11):e016349. doi: 10.1161/JAHA.120.016349. Epub 2020 May 22.
Ischemia/reperfusion injury is a complex molecular cascade that causes deleterious cellular damage and organ dysfunction. Stroke, sudden cardiac arrest, and acute myocardial infarction are the most common causes of ischemia/reperfusion injury without effective pharmacologic therapies. Existing preclinical evidence suggests that histone deacetylase inhibitors may be an efficacious, affordable, and clinically feasible therapy that can improve neurologic and cardiac outcomes following ischemia/reperfusion injury. In this review, we discuss the pathophysiology and epigenetic modulations of ischemia/reperfusion injury and focus on the neuroprotective and cardioprotective effects of histone deacetylase inhibitors. We also summarize the protective effects of histone deacetylase inhibitors for other vital organs and highlight the key research priorities for their successful translation to the bedside.
缺血/再灌注损伤是一种复杂的分子级联反应，会导致有害的细胞损伤和器官功能障碍。没有有效的药物治疗方法的情况下，中风、心搏骤停和急性心肌梗死是最常见的缺血/再灌注损伤的原因。现有的临床前证据表明，组蛋白去乙酰化酶抑制剂可能是一种有效、负担得起且在临床上可行的治疗方法，可以改善缺血/再灌注损伤后的神经和心脏结局。在这篇综述中，我们讨论了缺血/再灌注损伤的病理生理学和表观遗传调节，并重点介绍了组蛋白去乙酰化酶抑制剂的神经保护和心脏保护作用。我们还总结了组蛋白去乙酰化酶抑制剂对其他重要器官的保护作用，并强调了成功将其转化为临床应用的关键研究重点。
