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Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs.
DNA Cell Biol. 2007 Aug; 26(8):603-11.DC

Abstract

Homocysteine (Hcy) is a well-established risk factor for atherosclerosis and may cause dysregulation of gene expression, but the characteristics and the key links involved in its pathogenic mechanisms are still poorly understood. The aim of this study was to explore (i) the effects of Hcy on DNA methylation in vascular smooth muscle cells (VSMCs) and (ii) the underlying mechanism of Hcy-induced changes in DNA methylation patterns in relation to atherosclerosis. We examined the levels of gDNA methylation, namely, the Alu and line-1 element sequences, which can serve as a surrogate marker for gDNA methylation, and also investigated the effects of Hcy on the intracellular S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations as well as the expressions of SAH hydrolase (SAHH), DNA methyltransferase3a (DNMT3a), DNMT3b, and methyl-CpG-binding domain 2 (MBD2). We found that clinically relevant levels of Hcy (0-500 microM) induced elevation of SAH, declination of SAM and SAM/SAH ratio, and reduction in expression of SAHH and MBD2, but increased the activity of DNMT3a and DNMT3b compared to the control group (p < 0.05). We found also that the genome-wide hypomethylation is a common feature of gDNA in the VSMCs cultured with Hcy. In conclusion, these results suggest that Hcy-induced DNA methylation may be an important potential pathogenic mechanism in the development of atherosclerosis, and may become a therapeutic target for preventing Hcy-induced atherosclerosis.

Authors+Show Affiliations

Department of Pathophysiology, West China College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17688412

Citation

Yideng, Jiang, et al. "Homocysteine-mediated Expression of SAHH, DNMTs, MBD2, and DNA Hypomethylation Potential Pathogenic Mechanism in VSMCs." DNA and Cell Biology, vol. 26, no. 8, 2007, pp. 603-11.
Yideng J, Jianzhong Z, Ying H, et al. Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs. DNA Cell Biol. 2007;26(8):603-11.
Yideng, J., Jianzhong, Z., Ying, H., Juan, S., Jinge, Z., Shenglan, W., Xiaoqun, H., & Shuren, W. (2007). Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs. DNA and Cell Biology, 26(8), 603-11.
Yideng J, et al. Homocysteine-mediated Expression of SAHH, DNMTs, MBD2, and DNA Hypomethylation Potential Pathogenic Mechanism in VSMCs. DNA Cell Biol. 2007;26(8):603-11. PubMed PMID: 17688412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs. AU - Yideng,Jiang, AU - Jianzhong,Zhang, AU - Ying,Huang, AU - Juan,Su, AU - Jinge,Zhang, AU - Shenglan,Wang, AU - Xiaoqun,Han, AU - Shuren,Wang, PY - 2007/8/11/pubmed PY - 2007/10/3/medline PY - 2007/8/11/entrez SP - 603 EP - 11 JF - DNA and cell biology JO - DNA Cell Biol. VL - 26 IS - 8 N2 - Homocysteine (Hcy) is a well-established risk factor for atherosclerosis and may cause dysregulation of gene expression, but the characteristics and the key links involved in its pathogenic mechanisms are still poorly understood. The aim of this study was to explore (i) the effects of Hcy on DNA methylation in vascular smooth muscle cells (VSMCs) and (ii) the underlying mechanism of Hcy-induced changes in DNA methylation patterns in relation to atherosclerosis. We examined the levels of gDNA methylation, namely, the Alu and line-1 element sequences, which can serve as a surrogate marker for gDNA methylation, and also investigated the effects of Hcy on the intracellular S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations as well as the expressions of SAH hydrolase (SAHH), DNA methyltransferase3a (DNMT3a), DNMT3b, and methyl-CpG-binding domain 2 (MBD2). We found that clinically relevant levels of Hcy (0-500 microM) induced elevation of SAH, declination of SAM and SAM/SAH ratio, and reduction in expression of SAHH and MBD2, but increased the activity of DNMT3a and DNMT3b compared to the control group (p < 0.05). We found also that the genome-wide hypomethylation is a common feature of gDNA in the VSMCs cultured with Hcy. In conclusion, these results suggest that Hcy-induced DNA methylation may be an important potential pathogenic mechanism in the development of atherosclerosis, and may become a therapeutic target for preventing Hcy-induced atherosclerosis. SN - 1044-5498 UR - https://www.unboundmedicine.com/medline/citation/17688412/Homocysteine_mediated_expression_of_SAHH_DNMTs_MBD2_and_DNA_hypomethylation_potential_pathogenic_mechanism_in_VSMCs_ L2 - https://www.liebertpub.com/doi/full/10.1089/dna.2007.0584?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -