Promoter hypomethylation of microRNA223 gene is associated with atherosclerotic cerebral infarction.

Background And Aims: microRNA223 (miR-223) plays an important role in the development of atherosclerosis and ischemic stroke. It is involved in regulation of multiple physiological and pathophysiological processes such as cholesterol metabolism, endothelial cell (EC) function, and thrombosis. Here we investigated the role of methylation regulation of MIR-223 promoter region in atherosclerotic cerebral infarction (ACI) patients.

Methods: A total of 23 patients with ACI and 32 healthy individuals were recruited. We performed bisulfite sequencing PCR and real-time PCR to detect methylation levels of MIR-223 promoter region and miR-223, respectively, in genomic DNA isolated from peripheral blood leukocytes.

Results: Mean methylation levels of a total of nine CpGs of MIR-223 promoter were significantly lower in ACI patients than in healthy individuals (p < 0.01), and were also significantly lower in individuals with carotid atherosclerosis than those without carotid atherosclerosis (p < 0.05). Meanwhile, miR-223 expression in leukocytes was significantly higher in ACI patients than in healthy individuals (p < 0.05). miR-223 level was negatively correlated with mean methylation levels of MIR-223 promoter (r = -0.4451, p < 0.01). The methylation level of MIR-223 promoter revealed a positive correlation with the circulating total cholesterol level (r = 0.318, p = 0.019).

Conclusions: Hypomethylation of MIR-223 promoter is associated with atherosclerotic cerebral infarction.