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

过度压力过载导致代偿性心肌肥厚破坏的机制尚未完全阐明。我们之前描述过，低水平的IL-1是组成性产生的，IL-1诱导IGF-1维持压力过载下心肌细胞的稳态。在本报告中，我们讨论了控制代偿性肥厚向扩张性心力衰竭过渡的基因表达的表观遗传调控机制。结果，在代偿性肥厚到失代偿扩张型心力衰竭的过渡阶段，IGF-1启动子的甲基化增加。此外，体内给予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.