论文库首页  论文库
 
论文编号:
论文题目: DNA methylome analysis reveals distinct epigenetic patterns of ascending aortic dissection and bicuspid aortic valve
英文论文题目: DNA methylome analysis reveals distinct epigenetic patterns of ascending aortic dissection and bicuspid aortic valve
第一作者: Pan, S; Lai, H; Shen, YR; Breeze, C; Beck, S; Hong, T; Wang, CS; Teschendorff, AE
英文第一作者: Pan, S; Lai, H; Shen, YR; Breeze, C; Beck, S; Hong, T; Wang, CS; Teschendorff, AE
联系作者: Teschendorff, AE (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Teschendorff, AE (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2017
卷: 113
期: 6
页码: 692-704
摘要: Epigenetics may mediate the effects of environmental risk factors on disease, including heart disease. Thus, measuring the DNA methylome offers the opportunity to identify novel disease biomarkers and novel insights into disease mechanisms. The DNA methylation landscape of ascending aortic dissection (AD) and bicuspid aortic valve (BAV) with aortic aneurysmal dilatation remain uncharacterized. The present study aimed to explore the genome-wide DNA methylation landscape underpinning these two diseases. We used Illumina 450k DNA methylation beadarrays to analyse 21 ascending aorta samples, including 10 cases with AD, 5 with BAV and 6 healthy controls. We adjusted for intra-sample cellular heterogeneity, providing the first unbiased genome-wide exploration of the DNA methylation landscape underpinning these two diseases. We discover that both diseases are characterized by loss of DNA methylation at non-CpG sites. We validate this non-CpG hypomethylation signature with pyrosequencing. In contrast to non-CpGs, AD and BAV exhibit distinct DNA methylation landscapes at CpG sites, with BAV characterized mainly by hypermethylation of EZH2 targets. In the case of AD, integrative DNA methylation gene expression analysis reveals that AD is characterized by a dedifferentiated smooth muscle cell phenotype. Our integrative analysis further reveals hypomethylation associated overexpression of RARA in AD, a pattern which is also seen in cells exposed to smoke toxins. Our data supports a model in which increased cellular proliferation in AD and BAV underpins loss of methylation at non-CpG sites. Our data further supports a model, in which AD is associated with an inflammatory vascular remodeling process, possibly mediated by the epigenome and linked to environmental risk factors such as smoking.
英文摘要: Epigenetics may mediate the effects of environmental risk factors on disease, including heart disease. Thus, measuring the DNA methylome offers the opportunity to identify novel disease biomarkers and novel insights into disease mechanisms. The DNA methylation landscape of ascending aortic dissection (AD) and bicuspid aortic valve (BAV) with aortic aneurysmal dilatation remain uncharacterized. The present study aimed to explore the genome-wide DNA methylation landscape underpinning these two diseases. We used Illumina 450k DNA methylation beadarrays to analyse 21 ascending aorta samples, including 10 cases with AD, 5 with BAV and 6 healthy controls. We adjusted for intra-sample cellular heterogeneity, providing the first unbiased genome-wide exploration of the DNA methylation landscape underpinning these two diseases. We discover that both diseases are characterized by loss of DNA methylation at non-CpG sites. We validate this non-CpG hypomethylation signature with pyrosequencing. In contrast to non-CpGs, AD and BAV exhibit distinct DNA methylation landscapes at CpG sites, with BAV characterized mainly by hypermethylation of EZH2 targets. In the case of AD, integrative DNA methylation gene expression analysis reveals that AD is characterized by a dedifferentiated smooth muscle cell phenotype. Our integrative analysis further reveals hypomethylation associated overexpression of RARA in AD, a pattern which is also seen in cells exposed to smoke toxins. Our data supports a model in which increased cellular proliferation in AD and BAV underpins loss of methylation at non-CpG sites. Our data further supports a model, in which AD is associated with an inflammatory vascular remodeling process, possibly mediated by the epigenome and linked to environmental risk factors such as smoking.
刊物名称: CARDIOVASCULAR RESEARCH
英文刊物名称: CARDIOVASCULAR RESEARCH
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Cardiac & Cardiovascular Systems
英文学科: Cardiac & Cardiovascular Systems
影响因子: 5.878
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有