Hyperhomocysteinemia, DNA methylation and vascular disease

Jamaluddin, Saha; Yang, Xiaofeng; Wang, Hong

doi:10.1515/cclm.2007.350

Cited by 78 publications

(67 citation statements)

References 51 publications

(53 reference statements)

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“…Hcy has been demonstrated to induce both atherogenic and thrombogenic mediators in cultured vascular cells [20] and cause endothelial dysfunction in humans [21,22]. In fact, increasing synthesis of Hcy may have an effect on the progression of atherogenesis [23,24].…”

Section: Discussionmentioning

confidence: 99%

Total homocysteine levels and cardiovascular risk factors in healthy Tunisians

Oudi¹,

Aouni²,

Mazigh³

et al. 2011

East Mediterr Health J

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Hyperhomocysteinaemia is considered as an important independent risk factor for atherosclerosis and thrombotic disease. This study determined the distribution of homocysteine (Hcy) levels in healthy Tunisian subjects and evaluated the relationship between Hcy levels and some cardiovascular risk factors. Randomly selected subjects (592 men and 114 women) were recruited from different regions of Tunisia. The overall mean Hcy level was 12.6 (SD 5.4) µmol/L. Hcy levels in subjects with hyperhomocysteinaemia varied according to geographical region. Subjects with hyperhomocysteinaemia had significantly elevated total cholesterol, LDL cholesterol, apolipoprotein A and apolipoprotein B and lower vitamin B 12 levels compared with subjects with normohomocysteinaemia. Hcy levels correlated with total cholesterol (r = 0.09), apolipoprotein A (r = 0.012), and B (r = 0.013) levels and total/HDL cholesterol ratio (r = -0.085). Further epidemiological studies are needed to determine the precise role of Hcy in cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Total homocysteine levels and cardiovascular risk factors in healthy Tunisians

Oudi¹,

Aouni²,

Mazigh³

et al. 2011

East Mediterr Health J

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“…Hypermethylation of the estrogen receptor α (ER-α) promoter, and high plasma homocysteine levels, a source of the methyl group used for DNA methylation, were found in atherosclerosis patients (44,45). 5-Methylcytosine (5mC) is elevated in the intima of ApoE -/-mice fed a Western diet, and high 5mC levels are linked to LDL receptor and p53 mutation in vascular cells (43,46).…”

Section: Introductionmentioning

confidence: 99%

Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis

Dunn¹,

Qiu²,

Kim³

et al. 2014

J. Clin. Invest.

257

234

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“…Aberrant promoter hypermethylation of CpG islands associated with tumor suppressor gene (TSG) can lead to transcriptional silencing resulting in tumorigenesis (4). Epigenetic disorders give rise to several significant human diseases including various cancers, neuron disorder, psychosis, and cardiovascular diseases, many of which are mediated by altered DNA methyltransferase 1 (DNMT1) expression and activity (4)(5)(6)(7)(8)(9)(10). DNMT1 is one of the major enzymes responsible for DNA methylation (4).…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of p53/Sp1 Control Leads to DNA Methyltransferase-1 Overexpression in Lung Cancer

et al. 2010

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Overexpression of DNA 5′-cytosine-methyltransferases (DNMT), which are enzymes that methylate the cytosine residue of CpGs, is involved in many cancers. However, the mechanism of DNMT overexpression remains unclear. Here, we showed that wild-type p53 negatively regulated DNMT1 expression by forming a complex with specificity protein 1 (Sp1) protein and chromatin modifiers on the DNMT1 promoter. However, the stoichiometry between p53 and Sp1 determined whether Sp1 acts as a transcription activator or corepressor. Low level of exogenous Sp1 enhanced the repressive activity of endogenous p53 on the DNMT1 promoter whereas high level of Sp1 upregulated DNMT1 gene expression level in A549 (p53 wild-type) cells. In H1299 (p53 null) cells, exogenous Sp1 induced DNMT1 expression in a dose-dependent manner. We also discovered a new mechanism whereby high level of Sp1, via its COOH-terminal domain, induced interaction between p53 and MDM2, resulting in degradation of p53 by MDM2-mediated ubiquitination. Clinical data from 102 lung cancer patients indicated that overexpression of DNMT1 was associated with p53 mutation (P = 0.014) and high expression of Sp1 protein (P = 0.006). In addition, patients with overexpression of both DNMT1 and Sp1 proteins showed poor prognosis (P = 0.037). Our cell and clinical data provided compelling evidence that deregulation of DNMT1 is associated with gain of transcriptional activation of Sp1 and/or loss of repression of p53. DNMT1 overexpression results in epigenetic alteration of multiple tumor suppressor genes and ultimately leads to lung tumorigenesis and poor prognosis.

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Hyperhomocysteinemia, DNA methylation and vascular disease

Cited by 78 publications

References 51 publications

Total homocysteine levels and cardiovascular risk factors in healthy Tunisians

Total homocysteine levels and cardiovascular risk factors in healthy Tunisians

Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis

Dysregulation of p53/Sp1 Control Leads to DNA Methyltransferase-1 Overexpression in Lung Cancer

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