Homocysteine induces blood vessel global hypomethylation mediated by LOX-1

Yang, Xiaoming; Tian, Jianwei; J, C; Ai, Yang; Wang, J; Ma, S C; Cheng, Ying; Hua, Xin; Jiang, Yideng

doi:10.4238/2014.may.16.2

Cited by 26 publications

(15 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro experiments also showed that Hcy accelerated lipid accumulation in the foam cells. These results suggested that Hcy might promote the development of atherosclerosis as well as formation of the foam cells, which is in line with previously reported studies [4]. …”

Section: Discussionsupporting

confidence: 93%

“…Apo E-/- mice fed with methionine was a typical method to replicate hyperhomocysteinemia animal model [5]. Folic acid and vitamin B12 interfered Hcy production of methionine cycle [4, 8]. Increased lesions were observed in the HHcy group compared to the HLP group; moreover, when compared to HHcy+FA+VB group, the HHcy group demonstrated increased lesions (Fig 1A and 1B).…”

Section: Resultsmentioning

confidence: 99%

“…Homocysteine (Hcy), a toxic non-protein forming thiol-containing amino acid, is formed from methionine as a result of cellular methylation reactions [4]. Elevated plasma homocysteine levels are known to be a risk factor for atherosclerosis [5], resulting in cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation

Yang

Zhao

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases, such as atherosclerosis. HHcy promotes atherogenesis by modifying the histone methylation patterns and miRNA regulation. In this study, we investigated the effects of homocysteine (Hcy) on the expression of enhancer of zeste homolog 2 (EZH2), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased EZH2 expression, which is regulated by miR-92a. The levels of EZH2 and H3K27me3 were increased in the aorta of ApoE-/- mice fed a high-methionine diet for 16 weeks, whereas miR-92a expression was decreased. Over-expression of EZH2 increased H3K27me3 level and the accumulation of total cholesterol and triglycerides in the foam cells. Furthermore, upregulation of miR-92a reduced EZH2 expression in the foam cells. These data suggested that EZH2 plays a key role in Hcy-mediated lipid metabolism disorders, and that miR-92a may be a novel therapeutic target in Hcy-related atherosclerosis.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation

Yang

Zhao

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Folate had decreased hepatic SAH content but did not affect SAM content which resulted in higher SAM/SAH ratio. Reduced serum homocysteine and SAM had been previo u s l y o b s e r v e d i n h i g h -f a t d i e t -i n d u c e d hyperhomocysteinaemic ApoE −/− mice supplemented with folate and vitamin B 12 [47], while another study reported decreased plasma homocysteine but increased plasma SAM as well as SAM/SAH ratio in patients with hyperhomocysteinaemia [33]. Collectively, it can be said that folate increases methylation ratio, either by increasing SAM or decreasing SAH.…”

Section: Discussionmentioning

confidence: 97%

Palm tocotrienol-rich fraction inhibits methionine-induced cystathionine β-synthase in rat liver

et al. 2015

View full text Add to dashboard Cite

Oxidative stress plays an important role in cardiovascular diseases. The study investigated the effects of dietary palm tocotrienol-rich fraction on homocysteine metabolism in rats fed a high-methionine diet. Forty-two male Wistar rats were randomly assigned to six groups. Five groups were fed with high-methionine diet (1%) for 10 weeks. Groups 2 to 5 were also given dietary folate (8 mg/kg) and three doses of palm tocotrienol-rich fraction (30, 60 and 150 mg/kg) from week 6 to week 10. The last group was only given basal rat chow. High-methionine diet increased plasma homocysteine after 10 weeks, which was prevented by the supplementations of folate and high-dose palm tocotrienol-rich fraction. Hepatic S-adenosyl methionine (SAM) content was unaffected in all groups but S-adenosyl homocysteine (SAH) content was reduced in the folate group. Folate supplementation increased the SAM/SAH ratio, while in the palm tocotrienol-rich fraction groups, the ratio was lower compared with the folate. Augmented activity of hepatic cystathionine β-synthase and lipid peroxidation content by high-methionine diet was inhibited by palm tocotrienol-rich fraction supplementations (moderate and high doses), but not by folate. The supplemented groups had lower hepatic lipid peroxidation than the high-methionine diet. In conclusion, palm tocotrienol-rich fraction reduced high-methionine-induced hyperhomocysteinaemia possibly by reducing hepatic oxidative stress in high-methionine-fed rats. It may also exert a direct inhibitory effect on hepatic cystathionine β-synthase.

show abstract

“…In the processes of methionine metabolism, there are several byproducts, including Hcy, SAM and SAH, and previous studies have demonstrated that alterations in the SAM/SAH ratio may be more directly associated with vascular damage, compared with Hcy or the other intermediates (31)(32)(33). A number of studies have described that increased levels of Hcy are always followed by higher concentrations of SAH, and it may be an important mediator of toxicity in the body.…”

Section: Discussionmentioning

confidence: 99%

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

Zhang

Liu

et al. 2016

Mol Med Report

View full text Add to dashboard Cite

Abstract. The present study aimed to confirm whether the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) is a sensitive indicator, and whether it can be used as a biomarker for the clinical diagnosis of atherosclerosis. Apolipoprotein E (ApoE) -/-mice were randomly divided into four groups and fed with a high methionine diet for 15 weeks. Serum levels of homocysteine (Hcy) were measured using an automatic biochemistry analyzer. The concentrations of SAM and SAH were determined using high-performance liquid chromatography. The methylation levels of B1 repetitive elements, adipocyte fatty acid binding protein (FABP4), monocyte chemoattractant protein-1 (MCP-1) and extracellular superoxide dismutase (EC-SOD) were analyzed using nested touchdown-methylation-specific-polymerase chain reaction analysis. After 15 weeks, compared with the normal control group, serum concentrations of Hcy were significantly increased by 1.15-, 2.54-and 1.17-fold (P<0.05) in the ApoE -/-control group, Meth group and Meth-F group, respectively. The sizes of the atherosclerotic lesions were increased in the ApoE -/-control group, Meth group and Meth-F group, by up to 1.44-, 2.40-and 1.45-fold, respectively, compared with the normal control group (P<0.05). The concentrations of SAM were significantly increased by 3.02-, 3.42-and 2.46-fold in the ApoE -/-control group, Meth group and Meth-F group, respectively (P<0.05). The ratios of SAM/SAH were increased by 1.67-and 2.75-fold in the in ApoE -/-control group and Meth group, respectively, compared with the normal control group. The methylation levels of B1 repetitive elements, FABP4, MCP-1 and EC-SOD were decreased and exhibited hypomethylation. The methylation statuses of these genes were correlated with the ratio of the serum levels of SAM and SAH. These findings suggested that the SAM/SAH ratio is a biomarker and may provide a sensitive indicator for the clinical diagnosis of atherosclerosis.

show abstract

Homocysteine induces blood vessel global hypomethylation mediated by LOX-1

Cited by 26 publications

References 23 publications

Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation

Hyperhomocysteinemia in ApoE-/- Mice Leads to Overexpression of Enhancer of Zeste Homolog 2 via miR-92a Regulation

Palm tocotrienol-rich fraction inhibits methionine-induced cystathionine β-synthase in rat liver

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

Contact Info

Product

Resources

About