Abstract: Objective: To study the combined effects of hyperhomocysteinemia and hypercholesterolemia on genomic DNA methylation and DNA methyltransferase activity in aortic tissue of Wistar rats.Methods: 44 healthy clean level male Wistar rats were 2x2 factorial design randomized into four groups: negative control group, high-homocysteine group ， high-cholesterol group，High homocysteine mixed of high cholesterol group. The rats in negative control group were fed a normal chaw, and the other three groups were fed a chaw formula as designed.The rats were fed for three months. Heart blood was then drawn for detection of serum homocysteine and cholesterol; aortic genomic DNA was extracted for detection of genomic DNA methylation levels; and aortic nucleoprotein was extracted for detection of DNA methyltransferase activity.Results: Hyperhomocysteinemia combined effects of hypercholesterolemia increased serum homocysteine level， and there was significant statistics difference (P<0.01) ,make the performance for synergies，but there was no significant difference in rats total cholesterol (TC)、triglyceride (TG)、low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels by hyperhomocysteinemia combined effects of hypercholesterolemia (P>0.05). Hyperhomocysteinemia combined effects of hypercholesterolemia increased aortic genomic DNA methyltransferase activity ,and there was significant statistics difference(P<0.01) ,make the performance for synergies, and promoted aortic genomic DNA demethylation (P<0.01) ,make the performance for synergies effect.Conclusion: Hypomethylation and High-methyltransferase activity induced by hyperhomocysteinemia and the combined effects of hypercholesterolemia is one of the important mechanisms for the development of atherosclerosis.

Key words: atherosclerosis, hypercholesterolemia, hyperhomocysteinemia, DNA methyltransferases, DNA methylation