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

过度压力负荷下代偿性心肌肥厚的破坏机制尚未完全阐明。我们以前描述了低水平的IL-1是组成性产生的，IL-1诱导IGF-1维持压力超负荷下心肌细胞的稳态。在这份报告中，我们解决了表观遗传调控机制，以控制基因的表达，这是参与过渡的代偿性肥大扩张性心力衰竭。结果，在代偿性肥大向失代偿性扩张性心力衰竭的过渡阶段，IGF-1启动子甲基化增加。此外，体内施用DNA甲基转移酶抑制剂增加IGF-1的表达水平，并抑制代偿性肥大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.