英研究发现心力衰竭与DNA甲基化有关

2010-01-17 00:00 · Prima

英国研究人员日前报告说,他们首次发现DNA(脱氧核糖核酸)甲基化与心力衰竭之间存在关联,这一发现为治疗心力衰竭提供了新思路。 英国剑桥大学等机构研究人员在新一期美国网络期刊《公共科学图书馆综合》(PLoS One)上报告说,他们分析了心力衰竭晚期病人在心脏移植手术后留下的心脏组

英国研究人员日前报告说,他们首次发现DNA(脱氧核糖核酸)甲基化与心力衰竭之间存在关联,这一发现为治疗心力衰竭提供了新思路。

英国剑桥大学等机构研究人员在新一期美国网络期刊《公共科学图书馆综合》(PLoS One)上报告说,他们分析了心力衰竭晚期病人在心脏移植手术后留下的心脏组织样本,并将其与同龄因事故死亡者的健康心脏组织样本进行了对比,结果发现前者具有DNA甲基化的痕迹,而后者没有。

DNA甲基化是指DNA的构成单元之一胞嘧啶被选择性地添加甲基,这会使得DNA链条外形发生变化,导致一些蛋白质无法正确识别DNA,并且还有可能不正常地“开启”或“关闭”一些基因的功能。

研究人员说,此前的研究表明DNA甲基化与一些癌症密切相关,但这项研究第一次发现它和心力衰竭之间存在关联。由于DNA甲基化的过程受到环境和饮食影响,研究人员认为它是从环境因素到心力衰竭之间的“中间环节”,并有望据此找出治疗心力衰竭的新方法。


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《公共科学图书馆综合》发表论文摘要(英文)

Differential DNA Methylation Correlates with Differential Expression of Angiogenic Factors in Human Heart Failure

Mehregan Movassagh1, Mun-Kit Choy1, Martin Goddard2, Martin R. Bennett1, Thomas A. Down3, Roger S.-Y. Foo1*

Epigenetic mechanisms such as microRNA and histone modification are crucially responsible for dysregulated gene expression in heart failure. In contrast, the role of DNA methylation, another well-characterized epigenetic mark, is unknown. In order to examine whether human cardiomyopathy of different etiologies are connected by a unifying pattern of DNA methylation pattern, we undertook profiling with ischaemic and idiopathic end-stage cardiomyopathic left ventricular (LV) explants from patients who had undergone cardiac transplantation compared to normal control. We performed a preliminary analysis using methylated-DNA immunoprecipitation-chip (MeDIP-chip), validated differential methylation loci by bisulfite-(BS) PCR and high throughput sequencing, and identified 3 angiogenesis-related genetic loci that were differentially methylated. Using quantitative RT-PCR, we found that the expression of these genes differed significantly between CM hearts and normal control (p&0.01). Moreover, for each individual LV tissue, differential methylation showed a predicted correlation to differential expression of the corresponding gene. Thus, differential DNA methylation exists in human cardiomyopathy. In this series of heterogenous cardiomyopathic LV explants, differential DNA methylation was found in at least 3 angiogenesis-related genes. While in other systems, changes in DNA methylation at specific genomic loci usually precede changes in the expression of corresponding genes, our current findings in cardiomyopathy merit further investigation to determine whether DNA methylation changes play a causative role in the progression of heart failure.

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