DNA methylation inhibition attenuates pressure overload-induced cardiac hypertrophy in rats

Inhibitors of DNA methyl transferase (DNMT) might be useful for treating cardiac hypertrophy by preventing de novo methylation and reduced transcription of anti-hypertrophic genes. This approach had been tested, but without a detailed phenotypic and methylation analysis. Here, we subjected rats to pressure overload and treatment with the DNMT inhibitor N-phthalyl-L-tryptophan (RG108) and analysed DNA methylation by cardiomyocyte (CM)-specific reduced representation bisulphite sequencing (RRBS).DNA甲基转移酶（DNA methyl transferase, DNMT）抑制剂或可通过阻断抗心肌肥厚基因的从头甲基化并抑制其转录下调，用于治疗心肌肥厚。该策略此前已得到验证，但尚未开展详尽的表型与甲基化分析。本研究中，我们对大鼠构建压力负荷模型并给予DNMT抑制剂N-邻苯二甲酰-L-色氨酸（RG108）处理，随后通过心肌细胞（cardiomyocyte, CM）特异性限制性代表性亚硫酸氢盐测序（RRBS）分析其DNA甲基化水平。