Role of methylation of p21 gene in the proliferation of human vascular smooth muscle cells / 中国组织工程研究

ABSTRACT

BACKGROUND:Proliferation, migration and phenotypic changes of vascular smooth muscle cells is the core of the occurrence of atherosclerosis, and a series of related genes via methylation are involved in the process. OBJECTIVE:To investigate the effects of oxidized low density lipoprotein (ox-LDL) on DNA methylation in the promoter region of the p21 gene and its potential mechanism in the pathogenesis of atherosclerosis. METHODCultured human vascular smooth muscle cells were treated with different concentrations of ox-LDL (0, 10, 20, 40 mg/L) for 24 hours. The degree of DNA methylation was assayed by methylation-specific polymerase chain reaction, the expression of p21 mRNA was measured by reverse transcriptional polymerase chain reaction and the proliferative activity of vascular smooth muscle cells was determined by the MTT assay. RESULTS AND CONCLUSION:The ox-LDL treatment resulted in a promotion in the methylation in the promoter region of the p21 gene and a decrease in mRNA expression with a concentration-dependent manner;it also induced a dose-dependent promoting effect on vascular smooth muscle cellproliferation. The atherogenic mechanism of ox-LDL might promote vascular smooth muscle cellproliferation by the hypermethylation of the p21 gene that may lead to the occurrence and development of atherosclerosis.