Effect Of Rosuvastatin On Global DNA Methylation With Methionine-induced Hyperhomocysteinemia In Rats

Objective To investigate the effects of rosuvastatin on global DNAmethylation in rats with hyperhomocystinemia induced by ingestion of excessmethionine.Methods48healthy6-week-old wistar male rats, weighing(170±10g), afterbeing fed adaptable for a week,were randomly divided into control group(n=12)、hyperhomocysteinemia group(n=12)、rosuvastatin low dose treatment group(n=12)and rosuvastatin high dose treatment group(n=12). The control group was fed withAIN-93G diet, the hyperhomocysteinemia group was was pathogenic con-trol andreceived methionine(1g/kg, intragastric administration), the rosuvastatin lowdose treatment group received rosuvastatin(5mg/kg/d, intragastric administration)and the rosuvastatin high dose treatment group received rosuvastatin(10mg/kg/d,intragastric administration). After be maintained for20weeks on the previouslydescribed diets, the homocysteine concentrations in the plasma was measured withthe IMX assays. The thoracic aorta was harvested for morphology (HE staining).The DNA methyltransferase activity and global DNA methylation status of arotictissue was determained using an innovative enzyme-linked immunosorbent assay(ELISA).Results Our study showed the following:(a) A high methionine intragastricadministration for20weeks is sufficient to induce hyperhomocystinemia; rosuvastatin can prevent an elevation homocysteine (Hcy) levels in theplasma(P<0.01)and morphological changes in the thoracic aorta.(b) Comparedwith the Control group, the Hhcy group had decreased DNA MethyltransferaseActivity and global DNA methylation status(P<0.01,P<0.01).(c) Most important,after rosuvastatin supplementation, the lowering of Hcy levels was accompaniedby a marked elevation of DNA methyltransferase activity and global DNAmethylation status(P<0.01,P<0.05).Conclusion rosuvastatin supplementation can blunt the rise in Hcy but alsocan increase DNA methyltransferase activity and global DNA methylation status inthe aorta of rats with hyperhomocystinemia.