Unraveling the DNA methylome of atherosclerosis

Zaina, Silvio

doi:10.1097/mol.0000000000000059

Cited by 31 publications

(17 citation statements)

References 45 publications

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“…In particular, changes in DNA methylation patterns have been linked to several cardiovascular-related biomarkers, including homocysteine and C-reactive protein 9 . Furthermore, an increasing number of studies report DNA methylation alterations in atherosclerosis 24–26 . For example, a recent genome-wide study showed DNA methylation differences between healthy donor-matched aortic healthy and plaque tissue, indicated by epigenetic drift of DNA methylation in aortic plaques with atherosclerotic progression 22, 27 .…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease

Istas

Declerck

Pudenz

et al. 2017

Sci Rep

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Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses. Furthermore, a subset of 34 DMRs related to impaired oxidative stress, DNA repair, and inflammatory pathways could be replicated in an independent cohort study of donor-matched healthy and atherosclerotic human aorta tissue (n = 15) and human carotid plaque samples (n = 19). Upon integrated network analysis, BRCA1 and CRISP2 DMRs were identified as most central disease-associated DNA methylation biomarkers. Differentially methylated BRCA1 and CRISP2 regions were verified by MassARRAY Epityper and pyrosequencing assays and could be further replicated in blood, aorta tissue and carotid plaque material of atherosclerosis patients. Moreover, methylation changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with subclinical atherosclerosis measures (coronary calcium score and carotid intima media thickness) in an independent sample cohort of middle-aged men with subclinical cardiovascular disease in the Aragon Workers’ Health Study (n = 24). Altogether, BRCA1 and CRISP2 DMRs hold promise as novel blood surrogate markers for early risk stratification and CVD prevention.

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Section: Discussionmentioning

confidence: 99%

Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease

Istas

Declerck

Pudenz

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These novel concepts, for the first time, associate genetic variations with epigenetic changes. The interaction between genetic variants and DNA methylation also emphasize the need for an integrated study [8]. …”

Section: Introductionmentioning

confidence: 99%

Notable epigenetic role of hyperhomocysteinemia in atherogenesis

Zhou

Zhang

2014

Lipids Health Dis

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Atherosclerosis is associated with multiple genetic and modifiable risk factors. There is an increasing body of evidences to indicate that epigenetic mechanisms also play an essential role in atherogenesis by influencing gene expression. Homocysteine is a sulfur-containing amino acid formed during methionine metabolism. Elevated plasma level of homocysteine is generally termed as hyperhomocysteinemia. As a potential risk factor for cardiovascular diseases, hyperhomocysteinemia may initiate or motivate atherogenesis by modification of DNA methylation. The underlying epigenetic mechanism is still unclear with controversial findings. This review focuses on epigenetic involvement and mechanisms of hyperhomocysteinemia in atherogenesis. Considering the potential beneficial effects of anti-homocysteinemia treatments in preventing atherosclerosis, further studies on the role of hyperhomocysteinemia in atherogenesis are warranted.

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“…Previous studies showed that variations in Chr9p21 may increase the levels of ANRIL transcription, which in turn downregulate CDKN2A/2B expression and enhance cell proliferation, and subsequently promote atherosclerosis 14, 15) . Studies also confirmed that ANRIL could bind and recruit epigenetic modifiers to CDKN2A/2B and induce DNA methylation 16, 17) .…”

Section: Introductionmentioning

confidence: 78%

<i>CDKN2B</i> Methylation and Aortic Arch Calcification in Patients with Ischemic Stroke

Zhou

Cai

Zhang

et al. 2017

JAT

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Aim: CDKN2A/2B near chromosome 9p21 has been proposed as a potential genetic etiology for both atherosclerosis and arterial calcification. DNA methylation, which can change the expression of CDKN2A/2B, may be an underlying mechanism for this association. This study aimed to evaluate whether CDKN2A/2B methylation is related to aortic arch calcification (AAC) in patients with ischemic stroke.Methods: DNA methylation levels of CDKN2A/2B was measured using venous blood samples in 322 patients with ischemic stroke. A total of 36 CpG sites around promoter regions of CDKN2A/2B were examined. AAC was quantified with Agatston score based on results of computed tomography angiography.Results: There were 248 (77.0%) patients with and 74 (23.0%) patients without evident AAC. Compared with patients without AAC, patients with AAC had higher methylation levels of CDKN2B (5.72 vs 4.94, P < 0.001). Using a generalized linear model, positive correlation between methylation levels and log-transformed calcification scores was detected at CDKN2B (β = 0.275 ± 0.116, P = 0.018).Conclusion: Patients with higher levels of DNA methylation of CDKN2B may bear increased risk for AAC. Further studies to reveal the underlying mechanisms of this association are warranted for establishing a cause–effect relationship.

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Unraveling the DNA methylome of atherosclerosis

Abstract: Epigenetics continues to represent a promising area of research in atherosclerosis. The full exploitation of cutting edge epigenomics will be decisive to define whether epigenetics will contribute to lower the burden of cardiovascular diseases.

Cited by 31 publications

References 45 publications

Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease

Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease

Notable epigenetic role of hyperhomocysteinemia in atherogenesis

<i>CDKN2B</i> Methylation and Aortic Arch Calcification in Patients with Ischemic Stroke

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