Epigenetic analysis and establishment of novel therapy for heart failure

我们之前确定了心力衰竭特异性表观遗传标记，赖氨酸-4（K4 TM）或赖氨酸-9（K9 TM）上组蛋白H3的三甲基化，使用ChIP芯片分析Dahl盐敏感大鼠的左心室心肌细胞，这些大鼠对过量的盐摄入遗传不耐受。在这个项目中，我们研究是否给予组蛋白修饰酶的抑制剂，影响H3 K9的三甲基化状态改善左心室功能障碍或没有。失败阶段的左心室收缩通过施用H3 K9甲基转移酶抑制剂毛壳素而恢复。抑制剂有延长动物存活期的趋势。针对心力衰竭特异性表观遗传学改变的干预可能成为心力衰竭治疗的新策略。

We previously identified heart failure-specific epigenetic marks, trimethylation of histone H3 on lysine-4 (K4TM) or lysine-9 (K9TM) with using ChIP-on-chip analysis on the left ventricular cardiomyocytes of Dahl salt-sensitive rats which are genetically intolerant to excessive salt intake. In this project, we investigated whether administering an inhibitor of histone modifying enzyme which affects the trimethylation status on H3K9 ameliorates left ventricular dysfunction or not. Left ventricular contraction at failing stage has restored by administration of an inhibitor of H3K9 methyltransferase, Chaetocin. The inhibitor had a tendency to prolong survival term of animals. The intervention for heart failure-specific epigenetic alteration might become a novel therapeutic strategy for heart failure.