Homocysteine-mediated cholesterol efflux via &amp;lt;italic&amp;gt;ABCA1&amp;lt;/italic&amp;gt; and &amp;lt;italic&amp;gt;ACAT1&amp;lt;/italic&amp;gt; DNA methylation in THP-1 monocyte-derived foam cells

Yang, Xia; Ma, Li; Cai, Xin; Wang, Lei; Yang, Chia-Ming; Li, Guizhong; Zhang, Minghao; Sun, Weiwei; Jiang, Yideng

doi:10.1093/abbs/gms119

Cited by 34 publications

(35 citation statements)

References 42 publications

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“…We also provide additional validation of the independent associations with age and a proatherogenic lipid profile. As previously described, the relationship between dyslipidemia, CAD and higher DNA methylation levels at the ABCA1 gene promoter locus (associated with a lower ABCA1 gene expression) suggests that the ABCA1-driven reverse cholesterol transport is compromised when ABCA1 DNA methylation increases [7,14,15]. This could lead to an increased susceptibility to CAD as seen in Tangier disease or familial hypoalphalipoproteinemia [2,4].…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, we have recently shown that a higher DNA methylation level at the ABCA1 gene promoter locus was associated with lower HDL-C levels and a previous history of CAD in familial hypercholesterolemia (FH) [7]. Moreover, our group and others have shown that higher ABCA1 DNA methylation levels were associated with a lower ABCA1 gene expression [14,15]. All these previous results suggest that perturbations of the ABCA1 epigenetic profile might be a new molecular mechanism involved in CAD.…”

Section: Introductionmentioning

confidence: 99%

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Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men

et al. 2014

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BackgroundPrevious studies have suggested that DNA methylation contributes to coronary artery disease (CAD) risk variability. DNA hypermethylation at the ATP-binding cassette transporter A1 (ABCA1) gene, an important modulator of high-density lipoprotein cholesterol and reverse cholesterol transport, has been previously associated with plasma lipid levels, aging and CAD, but the association with CAD has yet to be replicated.ResultsABCA1 DNA methylation levels were measured in leucocytes of 88 men using bis-pyrosequencing. We first showed that DNA methylation at the ABCA1 gene promoter locus is associated with aging and CAD occurrence in men (P < 0.05). The latter association is stronger among older men with CAD (≥61 years old; n = 19), who showed at least 4.7% higher ABCA1 DNA methylation levels as compared to younger men with CAD (<61 years old; n = 19) or men without CAD (n = 50; P < 0.001). Higher ABCA1 DNA methylation levels in older men were also associated with higher total cholesterol (r = 0.34, P = 0.03), low-density lipoprotein cholesterol (r = 0.32, P = 0.04) and triglyceride levels (r = 0.26, P = 0.09). Furthermore, we showed that acetylsalicylic acid therapy is associated with 3.6% lower ABCA1 DNA methylation levels (P = 0.006), independent of aging and CAD status of patients.ConclusionsThis study provides new evidence that the ABCA1 epigenetic profile is associated with CAD and aging, and highlights that epigenetic modifications might be a significant molecular mechanism involved in the pathophysiological processes associated with CAD. Acetylsalicylic acid treatment for CAD prevention might involve epigenetic mechanisms.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men

et al. 2014

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“…Tessema and Belinsky (2008) identified that the SOAT2 promoter was methylated to varying degrees among a panel of lung cancer adenocarcinoma cells. Liang et al (2013) reported a modest decrease in SOAT1 promoter methylation following homocysteine treatment, which was contemporaneous with an increase in SOAT1 mRNA and cholesteryl ester concentration. Finally, Devlin et al (2010) reported that hepatic expression of Soat2 in hyperhomocystenemic mice was reduced in the context of elevated DNA methylation.…”

Section: Cholesterol Storagementioning

confidence: 89%

Epigenetic regulation of cholesterol homeostasis

Meaney

2014

Front. Genet.

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Although best known as a risk factor for cardiovascular disease, cholesterol is a vital component of all mammalian cells. In addition to key structural roles, cholesterol is a vital biochemical precursor for numerous biologically important compounds including oxysterols and bile acids, as well as acting as an activator of critical morphogenic systems (e.g., the Hedgehog system). A variety of sophisticated regulatory mechanisms interact to coordinate the overall level of cholesterol in cells, tissues and the entire organism. Accumulating evidence indicates that in additional to the more “traditional” regulatory schemes, cholesterol homeostasis is also under the control of epigenetic mechanisms such as histone acetylation and DNA methylation. The available evidence supporting a role for these mechanisms in the control of cholesterol synthesis, elimination, transport and storage are the focus of this review.

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“…Acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT1) promotes accumulation of CE in macrophages, thereby resulting in the foam cell formation, a hallmark of early atherosclerotic plaque. In the study by Liang et al [58], cultured monocyte-derived foam cells were incubated with clinical relevant concentrations of Hcy for 24 h. Number of foam cells and cholesterol level were increased, but the mRNA and protein expression of ABCA1 were decreased, while ACAT1 expression was increased in the presence of Hcy. The DNA methylation level of ABCA1 gene was increased whereas ACAT1 DNA methylation was decreased when Hcy concentrations were changed.…”

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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Homocysteine-mediated cholesterol efflux via <italic>ABCA1</italic> and <italic>ACAT1</italic> DNA methylation in THP-1 monocyte-derived foam cells

Cited by 34 publications

References 42 publications

Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men

Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men

Epigenetic regulation of cholesterol homeostasis

Notable epigenetic role of hyperhomocysteinemia in atherogenesis

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