The Effect of Shen-Yuan-Dan Capsule on Autophagy-Related Gene Atg13 Promoter Methylation and Genomic Methylation Levels in Atherosclerotic Mice.

BACKGROUND: Moderate autophagy plays a positive role in the prevention of atherosclerosis. Aberrant promoter methylation of autophagic genes can affect autophagy. Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, can prevent atherosclerosis in high-fat-fed mice. However, its precise mechanism remains unclear. This study investigated the mechanism of SYDC in ameliorating atherosclerosis in a mice model.

METHODS: After 6 weeks of a high-fat diet, apolipoprotein E knockout (apoE-/- ) mice were randomly grouped into control, Lipitor, and SYDC groups (n = 10). The mice were intragastrically administered with the respective drugs for 6 weeks. The expressions of Beclin1 and Atg5-Atg12 complex in atherosclerotic plaques of the mice were measured. The levels of 5-mC and DNA methyltransferase 1 (DNMT1) in the plasma of the mice were determined. The average methylation rate of CpG islands in the promoter region of autophagy-related protein (Atg13) and the mRNA expression of Atg13 in the aortas of the mice were determined.

RESULTS: SYDC up-regulated the expressions of Atg5-Atg12 complex and Beclin-1 in atherosclerotic plaques (p < 0.01). Moreover, SYDC decreased the 5-mC and DNMT1 levels in plasma and atherosclerotic plaques of the mice (p < 0.01), and also decreased the average methylation rate of CpG islands in the promoter region of Atg13 and increased the mRNA levels of Atg13 in the aortas of atherosclerotic mice (p < 0.01).

CONCLUSIONS: SYDC attenuates atherosclerosis by promoting autophagy, probably through regulating genomic DNA methylation and Atg13 promoter demethylation.