新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 表观遗传学 » PLoS One:心力衰竭与DNA甲基化有关

PLoS One:心力衰竭与DNA甲基化有关

来源:新华网 2010-01-15 17:25

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。(生物谷Bioon.com)

生物谷推荐原始出处:

PLoS ONE 5(1): e8564. doi:10.1371/journal.pone.0008564

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*

1 Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, University of Cambridge, Cambridge, United Kingdom, 2 Department of Histopathology, Papworth Hospital, Cambridge, United Kingdom, 3 Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom

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.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库