Finally, observation of different outcomes in hyperhomocysteinemic apoE−/− mice and both in PEMT−/−/Ldlr−/− and PEMT−/−/ApoE−/− mice suggests mechanisms besides inhibition of phospholipid methylation, for example, AdoHcy-dependent modulation of gene expression that may also contribute to the development of Hcy-dependent atherosclerosis. This evidence concerns the gene APOE and atherosclerosis.