Epigenetic regulation of gene expression related to compensated myocardial hypertrophy under pressure overload

过度压力超负荷破坏代偿性心肌肥厚的机制尚未完全阐明。我们以前曾描述过，低水平的IL-1是结构性产生的，IL-1诱导IGF-1在压力超负荷下维持心肌细胞的动态平衡。在这份报告中，我们讨论了表观遗传调控机制来控制基因的表达，这些基因参与了代偿性肥厚向扩张性心力衰竭的转变。结果，在代偿性肥厚到失代偿性扩张性心力衰竭的过渡期，IGF-1启动子的甲基化增加。此外，体内应用DNA甲基转移酶抑制剂可增加IGF-1的表达水平，并抑制代偿性肥厚向扩张性心力衰竭的转变。

The mechanism of disruption of compensated myocardial hypertrophy under excessive pressure overload has not been fully clarified. We previously described that low level of IL-1 is constitutively produced and IL-1 induce IGF-1 to maintain homeostasis of cardiomyocyte under pressure overload. In this report, we addressed the epigenetic regulatory mechanism to control expression of genes which is involved in the transition of compensated hypertrophy to dilated heart failure. As a result, during the transition phase of compensated hypertrophy to decompensated dilated heart failure, methylation of IGF-1 promoter was increased. Furthermore, in vivo administration of DNA methyl-transferase inhibitors increases expression level of IGF-1 and inhibited transition of compensated hypertrophy to dilated heart failure.