Hyperhomocysteinemia induced endothelial progenitor cells dysfunction through hyper-methylation of CBS promoter.

摘要: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are the key players in angiogenesis and vascular function. Cystathionine-β-synthase (CBS), an H2S-generating enzyme methionine metabolism, regulates function of these EPCs. This study aims to examine whether CBS hyper-methylation contributes bone cell (BM-EPCs) subsequent blood flow mice fed with a high diet (HMD). (BM) were collected from HMD control mice, differentiated into BM-EPCs, characterized by acLDL-DiI labeling. mRNA expression was analyzed real-time PCR, global methylation status promoter detected nuclear 5-mC assay methylation-specific PCR (qMSP) respectively. The result reveals that BM-EPCs hyper-methylated level was, indeed, negatively correlated angiogenic BM-EPCs. In addition, (5-mC) DNA methyltransferase-1 (DNMT1) increased condition. vitro also shows induced hyperhomocysteinemia (HHcy) impaired both adhesion properties accompanied higher compared control. Furthermore, found be decreased as wild-type mice. To dissect epigenetic mechanism, we administrated DNMT inhibitor, 5-azacytidine (5-Aza) administration 5-Aza restored expression, EPC mediated reducing abnormal hyper-methylation. conclusion, HHcy dismantles through