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

Hui Zhang, Yan Hua Wang, Sheng Chao Ma, Hui Zhang, An Ning Yang, Xiao Ling Yang, Ming Hao Zhang, Jian Min Sun, Yin Ju Hao, Yi Deng Jiang

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8 Citations (SciVal)

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 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.

Original languageEnglish
Pages (from-to)217-226
JournalExperimental Cell Research
Volume362
Issue number1
DOIs
Publication statusPublished - 2018

Subject classification (UKÄ)

  • Cell and Molecular Biology

Keywords

  • Cyclin A
  • DNA methylation
  • DNMT1
  • Endothelial progenitor cells
  • Homocysteine

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