Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients

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• 作者：Pan-Pan Niu (5)
  Yu Cao (6)
  Ting Gong (5)
  Jin-Hui Guo (7)
  Bi-Kui Zhang (5)
  Su-Jie Jia (5)
  
  5. Department of Pharmaceutics ; The Third Xiangya Hospital ; Central South University ; Tongzipo Road #138 ; Changsha ; 410013 ; China
  6. Department of Cardiology ; The Third Xiangya Hospital ; Central South University ; Changsha ; 410013 ; China
  7. Department of Pharmaceutics ; The First Affiliated Hospital ; Xinxiang Medical University ; Xinxiang ; 453100 ; China
  
• 关键词：Endothelial progenitor cells ; Atherosclerosis ; DNA methylation ; Dimethylarginine dimethylaminohydrolase ; Homocysteine
• 刊名：Journal of Translational Medicine
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：12
• 期：1
• 全文大小：746 KB
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• 刊物主题：Biomedicine general; Medicine/Public Health, general;
• 出版者：BioMed Central
• ISSN：1479-5876

文摘

Background Circulating endothelial progenitor cells (EPCs) may be a biomarker for vascular function and cardiovascular risk in patients with coronary artery disease (CAD). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) regulates the function of EPCs. This study aimed to examine whether hypermethylation of DDAH2 promoter contributes to impaired function of EPCs in CAD patients. Methods Peripheral blood mono-nuclear cells from 25 CAD patients and 15 healthy volunteers were collected and differentiated into EPCs. EPCs were tested for their adhesive capability. DDAH2 mRNA expression was analyzed by real-time PCR, and the methylation of DDAH2 promoter was detected by bisulfite genomic sequencing. Results DDAH2 promoter in EPCs from CAD patients was hypermethylated and the methylation level was negatively correlated to DDAH2 mRNA level and adhesion function of EPCs. Homocysteine impaired the adhesion function of EPCs, accompanied by lower DDAH2 expression and higher methylation level of DDAH2 promoter, compared to controls. These effects of homocysteine were reversed by pretreatment with Aza, an inhibitor of DNA methyltransferase. Conclusion Hypermethylation in DDAH2 promoter is positively correlated to the dysfunction of EPCs in CAD patients. Homocysteine disrupts EPCs function via inducing the hypermethylation of DDAH2 promoter, suggesting a key role of epigenetic mechanism in the progression of atherosclerosis.