Assessment of global DNA methylation in human atherosclerosis using methylation of retrotransposable element LINE-1

Rationale. Atherosclerosis is a complex age-dependent disease developed under contribution of epigenetic factors. Decreasing of global DNA methylation, estimated by methylation level of retrotransposon LINE-1 in blood leukocytes is associated with a risk of complications of atherosclerosis, but epigenetic status of LINE-1 in the lesion of artery wall is under-investigated. Aim. Analysis of the global DNA methylation variability (using methylation level of LINE-1) in human blood cells and carotid arteries in atherosclerosis. Materials and methods. Quantification of LINE-1 methylation level in match pairs of carotid arteries affected by atherosclerosis and blood leukocytes collected from patients (n = 92), as well as in white blood cells of the same-aged healthy individuals (n = 60) was performed using bisulfite pyrosequencing. Results. Global DNA methylation estimated as LINE-1 methylation level was lower in blood leukocytes of patients with advanced carotid atherosclerosis (66.2%) in comparison with healthy individuals (68.2%; p<0.05). Further decrease of LINE-1 methylation level was observed in cells of carotid atherosclerotic lesions compared to matched samples of blood leukocytes (64.8% vs. 66.2%, respectively, p<0.05). LINE-1 methylation level was negatively correlated with the chronological age of healthy individuals, as well as with the body mass index and the atherogenic index of both healthy individuals and patients with advanced carotid atherosclerosis. Conclusion. The decrease of global DNA methylation estimated as hypomethylation of LINE-1 in blood leukocytes and arterial cells was associated with advanced carotid atherosclerosis and its risk factors.

атеросклероз, метилирование ДНК, мобильный генетический элемент, ретротранспозон, LINE-1, atherosclerosis, DNA methylation, transposable element, retrotransposon, LINE-1

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