To examine the relationship between hyperhomocysteinemia (HHcy) and the progression of atherosclerosis, Apolipoprotein-E-deficient (apoE−/−) mice—an established pre-clinical model for this human pathology—were assigned to either a hyperhomocysteinemic diet (HHD) deficient in methyl donors and B vitamins or a control diet (CD) containing sufficient levels of micronutrients. Here, APOE is linked to hyperhomocysteinemia.