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Homocysteine inhibits endothelial progenitor cells proliferation via DNMT1-mediated hypomethylation of Cyclin A

Zhang, Hui LU ; Wang, Yan Hua; Ma, Sheng Chao; Zhang, Hui LU ; Yang, An Ning; Yang, Xiao Ling; Zhang, Ming Hao; Sun, Jian Min LU ; Hao, Yin Ju and Jiang, Yi Deng (2017) In Experimental Cell Research
Abstract

Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner. Knockdown of Cyclin A prominently reduced proliferation of EPCs, while over-expression of Cyclin A significantly promoted the cell proliferation, suggesting that Hcy inhibits EPCs proliferation through downregulation... (More)

Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner. Knockdown of Cyclin A prominently reduced proliferation of EPCs, while over-expression of Cyclin A significantly promoted the cell proliferation, suggesting that Hcy inhibits EPCs proliferation through downregulation of Cyclin A expression. In addition, epigenetic study also demonstrated that Hcy induces DNA hypomethylation of the Cyclin A promoter in EPCs through downregulated expression of DNMT1. Moreover, we found that Hcy treatment of EPCs leads to increased SAM, SAH and MeCP2, while the ratio of SAM/SAH and MBD expression decrease. In summary, our results indicate that Hcy inhibits Cyclin A expression through hypomethylation of Cyclin A and thereby suppress EPCs proliferation. These findings demonstrate a novel mechanism of DNA methylation mediated by DNMT1 in prevention of Hcy associated cardiovascular disease.

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author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Cyclin A, DNA methylation, DNMT1, Endothelial progenitor cells, Homocysteine
in
Experimental Cell Research
publisher
Academic Press
external identifiers
  • scopus:85035361800
ISSN
0014-4827
DOI
10.1016/j.yexcr.2017.11.021
language
English
LU publication?
yes
id
e2ca4568-ec02-47e7-932f-74e6ec4049e5
date added to LUP
2017-12-12 15:04:33
date last changed
2018-01-07 12:28:31
@article{e2ca4568-ec02-47e7-932f-74e6ec4049e5,
  abstract     = {<p>Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner. Knockdown of Cyclin A prominently reduced proliferation of EPCs, while over-expression of Cyclin A significantly promoted the cell proliferation, suggesting that Hcy inhibits EPCs proliferation through downregulation of Cyclin A expression. In addition, epigenetic study also demonstrated that Hcy induces DNA hypomethylation of the Cyclin A promoter in EPCs through downregulated expression of DNMT1. Moreover, we found that Hcy treatment of EPCs leads to increased SAM, SAH and MeCP2, while the ratio of SAM/SAH and MBD expression decrease. In summary, our results indicate that Hcy inhibits Cyclin A expression through hypomethylation of Cyclin A and thereby suppress EPCs proliferation. These findings demonstrate a novel mechanism of DNA methylation mediated by DNMT1 in prevention of Hcy associated cardiovascular disease.</p>},
  author       = {Zhang, Hui and Wang, Yan Hua and Ma, Sheng Chao and Zhang, Hui and Yang, An Ning and Yang, Xiao Ling and Zhang, Ming Hao and Sun, Jian Min and Hao, Yin Ju and Jiang, Yi Deng},
  issn         = {0014-4827},
  keyword      = {Cyclin A,DNA methylation,DNMT1,Endothelial progenitor cells,Homocysteine},
  language     = {eng},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Homocysteine inhibits endothelial progenitor cells proliferation via DNMT1-mediated hypomethylation of Cyclin A},
  url          = {http://dx.doi.org/10.1016/j.yexcr.2017.11.021},
  year         = {2017},
}