Research on the relative risk factors for genomic DNA methylation in Wistar rats

Abstract:

To discuss the effect of hyperhomocysteinemia（HHCY） and hypercholesterolemia（HTC） on genomic DNA methylation and DNA methyltransferase activity in aortic tissue of Wistar rats and to compare their differences. Methods：Totally 33 Wistar rats were equally randomized into three groups：control group，methionine group and high-cholesterol group（n=11）. The rats in control group were fed with normal chaw while those in the other two groups were fed with formula chaw for three months. Heart blood was drawn to detect the serum homocysteine（Hcy） and total cholesterol（TC）. Aortic genomic DNA was extracted to detect genomic DNA methylation levels and aortic nucleoprotein was extracted to detect DNA methyltransferase activity. Results：The results of Dunnett-t test showed that serum TC level was significantly higher in high-cholesterol group than in control and methionine groups（P＜0.05），but there was no statistically significant difference in triglyceride（TG），low density lipoprotein cholesterol（LDL-C） and high density lipoprotein cholesterol（HDL-C） levels between high-cholesterol group and the other two groups（P ＞0.05）. Serum Hcy was significantly higher in methionine group than in high-cholesterol and control groups（P＜0.05）. Compared with control group，HHCY and HTC significantly increased DNA methyltransferase activity and promoted DNA demethylation in both high-cholesterol and methionine groups（P＜0.05），though there was no significant difference between high-cholesterol and methionine groups（P ＞0.05）. Conclusions：Hypomethylation induced by HTC is one of the important mechanisms for the development of atherosclerosis. There is no significant difference between HHCY and HTC in leading hypomethylation.