Differential effects of nutritional folic acid deficiency and moderate hyperhomocysteinemia on aortic plaque formation and genome-wide DNA methylation in vascular tissue from ApoE-/- mice

摘要: Low folate intake is associated with vascular disease. Causality has been attributed to hyperhomocysteinemia. However, human intervention trials have failed show the benefit of homocysteine-lowering therapies. Alternatively, low may promote disease by deregulating DNA methylation. We investigated whether could alter methylation and atherosclerosis in ApoE null mice. Mice were fed one six diets (n = 20 per group) for 16 weeks. Basal either control (C; 4% lard) or high fat (HF; 21% lard cholesterol, 0.15%) different B-vitamin compositions: (1) folic acid replete, (2) deficient (−F), (3) acid, B6 B12 (−F−B). −F decreased plasma (up 85%; P < 0.05), whole blood 70%; liver 65%; P < 0.05) hepatic SAM/SAH 80%; P < 0.05). −F−B reduced 76%; 72%; 39%; 90%; increased homocysteine 2-fold, while 3.6- 6.8-fold C HF groups (P < 0.05). Plaque formation was 2-fold (P < 0.0001) mice a diet. Feeding HF–F diet lesion 17% There no change 5-methyldeoxycytidine tissue (aorta, periadventitial heart). These data suggest that atherogenesis not genome-wide epigenetic changes this animal model.